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Blair BA, Bragdon E, Dhillon G, Baker N, Stasiak L, Muthig M, Miramon P, Lorenz MC, Wheeler RT. Forward genetic screen in zebrafish identifies new fungal regulators that limit host-protective Candida-innate immune interaction. mBio 2025; 16:e0052925. [PMID: 40172223 PMCID: PMC12077120 DOI: 10.1128/mbio.00529-25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Accepted: 02/27/2025] [Indexed: 04/04/2025] Open
Abstract
Candida is one of the most frequent causes of bloodstream infections, and our first line of defense against these invasive infections is the innate immune system. The early immune response is critical in controlling Candida albicans infection, but C. albicans has several strategies to evade host immune attack. Phagocytosis of C. albicans blocks hyphal growth, limiting host damage and virulence, but how C. albicans limits early recruitment and phagocytosis in vertebrate infection is poorly understood. To study innate immune evasion by intravital imaging, we utilized the transparent larval zebrafish infection model to screen 131 C. albicans mutants for altered virulence and phagocyte response. Infections with each of the seven hypovirulent mutants led to altered phagocyte recruitment and/or phagocytosis, falling into four categories. Of particular interest among these is NMD5, a predicted β-importin and newly identified virulence factor. The nmd5∆/∆ mutant fails to limit phagocytosis, and its virulence defects are eliminated when phagocyte activity is compromised, suggesting that its role in virulence is limited to immune evasion. These quantitative intravital imaging experiments are the first to document altered Candida-phagocyte interactions for several additional mutants and clearly distinguish recruitment from phagocytic uptake, suggesting that Candida modulates both events. This initial large-scale screen of individual C. albicans mutants in a vertebrate, coupled with high-resolution imaging of Candida-phagocyte interactions, provides a more nuanced view of how diverse mutations can lead to more effective phagocytosis, a key immune process that blocks germination and drives anti-fungal immunity. IMPORTANCE Candida albicans is part of the human microbial community and is a dangerous opportunistic pathogen, able to prevent its elimination by the host immune system. Although Candida avoids immune attack through several strategies, we still understand little about how it regulates when immune phagocytes get recruited to the infection site and when they engulf fungal cells. We tested over 130 selected Candida mutants for their ability to cause lethal infection and found several hypovirulent mutants, which provoked altered innate immune responses, resulting in lower overall inflammation and greater host survival. Of particular interest is NMD5, which acts to limit fungal phagocytosis and is predicted to regulate the activity of stress-associated transcription factors. Our high-content screening was enabled by modeling Candida infection in transparent vertebrate zebrafish larva. Our findings help us understand how Candida survives immune attack during commensal and pathogenic growth, and may eventually inform new strategies for controlling disease.
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Affiliation(s)
- Bailey A. Blair
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, Maine, USA
- Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA
| | - Emma Bragdon
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, Maine, USA
| | - Gursimran Dhillon
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, Maine, USA
| | - Nnamdi Baker
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, Maine, USA
| | - Lena Stasiak
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, Maine, USA
| | - Mya Muthig
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, Maine, USA
| | - Pedro Miramon
- Department of Microbiology and Molecular Genetics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Michael C. Lorenz
- Department of Microbiology and Molecular Genetics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Robert T. Wheeler
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, Maine, USA
- Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA
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Wattanasuntorn P, Poapolathep S, Phuektes P, Alassane-Kpembi I, Fink-Gremmels J, Oswald IP, Poapolathep A. Apoptotic Effect of Combinations of T-2, HT-2, and Diacetoxyscirpenol on Human Jurkat T Cells. Toxins (Basel) 2025; 17:203. [PMID: 40278701 PMCID: PMC12030997 DOI: 10.3390/toxins17040203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 04/09/2025] [Accepted: 04/16/2025] [Indexed: 04/26/2025] Open
Abstract
Trichothecene type A mycotoxins, such as T-2, HT-2, and diacetoxyscirpenol (DAS), are known to induce cytotoxicity and apoptosis in different cell types. As all three Fusarium toxins may occur concomitantly in a given food or feed commodity, there is growing interest in the effect of such mycotoxin mixtures. This study aimed to identify the toxic interactions among T-2, HT-2, and DAS in a human Jurkat cell model. As a first step, an MTT assay was used to assess cytotoxicity after 24 h of cell exposure to individual mycotoxins and their mixtures. The results were used to calculate the combination index (CI), which indicates the nature of the mycotoxin interactions. In Jurkat T cells, the toxicity ranking for the individual mycotoxins was T-2 > HT-2 > DAS. The CI values of the dual and triple mycotoxin combinations calculated from the results of the MTT and reactive oxygen species assays showed synergistic effects at low concentrations and an apparent antagonism at very high concentrations for all combinations. The additional cytometric analyses confirmed the synergistic effects, as expected, following co-exposure to the three tested trichothecenes. As the lower toxin concentrations investigated reflect natural contamination levels in food and feeds, the synergistic effects identified should be considered in risk characterization for trichothecene exposure in humans and animals.
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Affiliation(s)
- Phattarawadee Wattanasuntorn
- Interdisciplinary Graduate Program in Genetic Engineering, Graduate School, Kasetsart University, Bangkok 10900, Thailand;
| | - Saranya Poapolathep
- Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand;
| | - Patchara Phuektes
- Department of Pathobiology, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen 40002, Thailand;
| | - Imourana Alassane-Kpembi
- Department of Veterinary Biomedicine, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, QC J2R 0A8, Canada;
| | - Johanna Fink-Gremmels
- Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, 3508 Utrecht, The Netherlands;
| | - Isabelle P. Oswald
- Toxalim (Research Centre in Food Toxicology), Toulouse University, INRAE, ENVT, INP-Purpon, UPS, 31000 Toulouse, France;
| | - Amnart Poapolathep
- Interdisciplinary Graduate Program in Genetic Engineering, Graduate School, Kasetsart University, Bangkok 10900, Thailand;
- Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand;
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Hayes WK, Gren ECK, Nelsen DR, Corbit AG, Cooper AM, Fox GA, Streit MB. It's a Small World After All: The Remarkable but Overlooked Diversity of Venomous Organisms, with Candidates Among Plants, Fungi, Protists, Bacteria, and Viruses. Toxins (Basel) 2025; 17:99. [PMID: 40137872 PMCID: PMC11945383 DOI: 10.3390/toxins17030099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/15/2025] [Accepted: 02/18/2025] [Indexed: 03/29/2025] Open
Abstract
Numerous organisms, including animals, plants, fungi, protists, and bacteria, rely on toxins to meet their needs. Biological toxins have been classified into three groups: poisons transferred passively without a delivery mechanism; toxungens delivered to the body surface without an accompanying wound; and venoms conveyed to internal tissues via the creation of a wound. The distinctions highlight the evolutionary pathways by which toxins acquire specialized functions. Heretofore, the term venom has been largely restricted to animals. However, careful consideration reveals a surprising diversity of organisms that deploy toxic secretions via strategies remarkably analogous to those of venomous animals. Numerous plants inject toxins and pathogenic microorganisms into animals through stinging trichomes, thorns, spines, prickles, raphides, and silica needles. Some plants protect themselves via ants as venomous symbionts. Certain fungi deliver toxins via hyphae into infected hosts for nutritional and/or defensive purposes. Fungi can possess penetration structures, sometimes independent of the hyphae, that create a wound to facilitate toxin delivery. Some protists discharge harpoon-like extrusomes (toxicysts and nematocysts) that penetrate their prey and deliver toxins. Many bacteria possess secretion systems or contractile injection systems that can introduce toxins into targets via wounds. Viruses, though not "true" organisms according to many, include a group (the bacteriophages) which can inject nucleic acids and virion proteins into host cells that inflict damage rivaling that of conventional venoms. Collectively, these examples suggest that venom delivery systems-and even toxungen delivery systems, which we briefly address-are much more widespread than previously recognized. Thus, our understanding of venom as an evolutionary novelty has focused on only a small proportion of venomous organisms. With regard to this widespread form of toxin deployment, the words of the Sherman Brothers in Disney's iconic tune, It's a Small World, could hardly be more apt: "There's so much that we share, that it's time we're aware, it's a small world after all".
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Affiliation(s)
- William K. Hayes
- Department of Earth and Biological Sciences, Loma Linda University, Loma Linda, CA 92350, USA; (A.M.C.); (G.A.F.); (M.B.S.)
| | - Eric C. K. Gren
- Bitterroot College, University of Montana, Hamilton, MT 59840, USA;
| | - David R. Nelsen
- Biology/Allied Health Department, Southern Adventist University, Collegedale, TN 37315, USA; (D.R.N.); (A.G.C.)
| | - Aaron G. Corbit
- Biology/Allied Health Department, Southern Adventist University, Collegedale, TN 37315, USA; (D.R.N.); (A.G.C.)
| | - Allen M. Cooper
- Department of Earth and Biological Sciences, Loma Linda University, Loma Linda, CA 92350, USA; (A.M.C.); (G.A.F.); (M.B.S.)
| | - Gerad A. Fox
- Department of Earth and Biological Sciences, Loma Linda University, Loma Linda, CA 92350, USA; (A.M.C.); (G.A.F.); (M.B.S.)
| | - M. Benjamin Streit
- Department of Earth and Biological Sciences, Loma Linda University, Loma Linda, CA 92350, USA; (A.M.C.); (G.A.F.); (M.B.S.)
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Blair BA, Bragdon E, Dhillon G, Baker N, Stasiak L, Muthig M, Miramon P, Lorenz MC, Wheeler RT. Forward genetic screen in zebrafish identifies new fungal regulators that limit host-protective Candida-innate immune interaction. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.02.14.638315. [PMID: 39990375 PMCID: PMC11844468 DOI: 10.1101/2025.02.14.638315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/25/2025]
Abstract
Candida is one of the most frequent causes of bloodstream infections, and our first line of defense against these invasive infections is the innate immune system. The early immune response is critical in controlling C. albicans infection, but C. albicans has several strategies to evade host immune attack. Phagocytosis of C. albicans blocks hyphal growth, limiting host damage and virulence, but how C. albicans limits early recruitment and phagocytosis in vertebrate infection is poorly understood. To study innate immune evasion by intravital imaging, we utilized the transparent larval zebrafish infection model to screen 131 C. albicans mutants for altered virulence and phagocyte response. Infections with each of seven hypovirulent mutants led to altered phagocyte recruitment and/or phagocytosis, falling into four categories. Of particular interest among these is NMD5, a predicted β-importin and newly-identified virulence factor. The nmd5∆/∆ mutant fails to limit phagocytosis and its virulence defects are eliminated when phagocyte activity is compromised, suggesting that its role in virulence is limited to immune evasion. These quantitative intravital imaging experiments are the first to document altered Candida-phagocyte interactions for several additional mutants, and clearly distinguish recruitment from phagocytic uptake, suggesting that Candida modulates both events. This initial large-scale screen of individual C. albicans mutants in a vertebrate, coupled with high-resolution imaging of Candida-phagocyte interactions, provides a more nuanced view of how diverse mutations can lead to more effective phagocytosis, a key immune process which blocks germination and drives anti-fungal immunity.
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Affiliation(s)
- Bailey A. Blair
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME 04469
- Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469
| | - Emma Bragdon
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME 04469
| | - Gursimran Dhillon
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME 04469
| | - Nnamdi Baker
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME 04469
| | - Lena Stasiak
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME 04469
| | - Mya Muthig
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME 04469
| | - Pedro Miramon
- Department of Microbiology and Molecular Genetics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA
| | - Michael C. Lorenz
- Department of Microbiology and Molecular Genetics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA
| | - Robert T. Wheeler
- Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME 04469
- Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469
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Sarturi JA, Simões CT, Rosa da Silva C, Laber IF, Medianeira de Lima Schlösser L, Carossi Leal LM, Konradt G, Bassuino DM, Mallmann CA. Development of an ex vivo model to assess the impact of fumonisin B 1 on swine intestinal morphology. Toxicon 2025; 255:108249. [PMID: 39800076 DOI: 10.1016/j.toxicon.2025.108249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 12/17/2024] [Accepted: 01/10/2025] [Indexed: 01/15/2025]
Abstract
This study was conducted to assess the effects of fumonisin B1 (FB1) on the jejunum of pigs using a novel ex vivo model conducted in parallel with an in vivo trial. For the in vivo model, twelve male 28 to 70-days-old pigs were subjected to two treatments of six animals each: the control group, fed a basal diet (BD), and the FB1 group, fed the BD + 50 mg/kg FB1. At 70 days, the animals were slaughtered and one jejunal sample was collected from each pig for further histopathological analyses. Other four male pigs from the in vivo control treatment were slaughtered at 70 days for the ex vivo model. Four jejunal explants were collected from each pig, totaling 16 intestinal explants, which were subjected to two treatments, with 8 explants each, using an Ussing Chamber (UC) system: the control group, subjected to buffer solution (BS), and the FB1 group, subjected to BS + 50 mg/L FB1. Samples from in vivo and ex vivo models were analyzed for histopathological parameters and subjective intestinal assessments. The FB1 group presented lower (P < 0.05) villi height than the control group in both in vivo and ex vivo. A decrease (P < 0.05) in the villi number, crypt depth, enterocyte height and enterocyte nucleus size was also observed in the FB1 group ex vivo, with a higher severity score of lymphatic vessels dilation than the control (P = 0.0459). The FB1 group also tended to increase the goblet cells count (P = 0.0736) ex vivo as well as to decrease the crypt width (P = 0.0638) in vivo. The ex vivo model exhibited similar mean values and statistical responses to those observed in vivo, demonstrating its potential as an alternative approach for assessing the effects of mycotoxins in a reduced number of animals.
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Affiliation(s)
- Janine Alves Sarturi
- Federal University of Santa Maria, Laboratory of Mycotoxicological Analyses, Santa Maria, Rio Grande do Sul, Brazil
| | - Cristina Tonial Simões
- Federal University of Santa Maria, Laboratory of Mycotoxicological Analyses, Santa Maria, Rio Grande do Sul, Brazil
| | - Cristiane Rosa da Silva
- Federal University of Santa Maria, Laboratory of Mycotoxicological Analyses, Santa Maria, Rio Grande do Sul, Brazil
| | - Isadora Fabris Laber
- Federal University of Santa Maria, Laboratory of Mycotoxicological Analyses, Santa Maria, Rio Grande do Sul, Brazil
| | | | | | - Guilherme Konradt
- Konradt Veterinary Diagnostics, São Martinho, Rio Grande do Sul, Brazil
| | - Daniele Mariath Bassuino
- Konradt Veterinary Diagnostics, São Martinho, Rio Grande do Sul, Brazil; Universidade La Salle, Canoas, Rio Grande do Sul, Brazil
| | - Carlos Augusto Mallmann
- Federal University of Santa Maria, Laboratory of Mycotoxicological Analyses, Santa Maria, Rio Grande do Sul, Brazil.
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Ziarati M, Imani A, Ghafarifarsani H, Bhatt D. A Brief Review on Aflatoxicosis in Aquaculture With a Focus on Fish. AQUACULTURE NUTRITION 2024; 2024:3130230. [PMID: 39713178 PMCID: PMC11663045 DOI: 10.1155/anu/3130230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Accepted: 11/09/2024] [Indexed: 12/24/2024]
Abstract
Feed quality is among the most determinative criteria for aquaculture success. Along with feed ingredient quality and its production process, feed storage conditions would also affect feed quality, especially in terms of adventitious toxins. Mycotoxins are frequent food and feed contaminants and are considered important health threats to both human and animal health. In this context, the effects of mycotoxins on aquatic animals were reviewed with an emphasis on aflatoxin B1 (AFB1), which is obviously reported in aquafeed. Severe tissue damage, increased susceptibility to infectious diseases, compromised immune system function, and increasing unknown death risks are among the most frequent symptoms of aflatoxicosis in aquatic animals. The lowest observable effect level for AFB1 has also been documented for different fish species. Considering the importance of such fungal toxins on the economic viability of aquaculture enterprises, it is recommended that further knowledge be obtained concerning the safe levels of AFB1 in terms of fish health and final product safety to human consumers.
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Affiliation(s)
- Mina Ziarati
- Department of Microbiology, National Center for Survey and Disease Diagnosis, Iranian Veterinary Organization (IVO), Bushehr, Iran
| | - Ahmad Imani
- Department of Fisheries, Faculty of Natural Resources, Urmia University, Urmia, Iran
| | - Hamed Ghafarifarsani
- Department of Animal Science, Chaharmahal and Bakhtiari Agricultural and Natural Resources Research and Education Center, Agricultural Research, Education and Extension Organization (AREEO), Shahrekord, Iran
| | - Deepa Bhatt
- Department of Aquaculture, College of Fisheries, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, India
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de Hoog S, Tang C, Zhou X, Jacomel B, Lustosa B, Song Y, Kandemir H, A Ahmed S, Zhou S, Belmonte-Lopes R, Quan Y, Feng P, A Vicente V, Kang Y. Fungal primary and opportunistic pathogens: an ecological perspective. FEMS Microbiol Rev 2024; 48:fuae022. [PMID: 39118380 PMCID: PMC11409879 DOI: 10.1093/femsre/fuae022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 06/02/2024] [Accepted: 08/07/2024] [Indexed: 08/10/2024] Open
Abstract
Fungal primary pathogenicity on vertebrates is here described as a deliberate strategy where the host plays a role in increasing the species' fitness. Opportunism is defined as the coincidental survival of an individual strain in host tissue using properties that are designed for life in an entirely different habitat. In that case, the host's infection control is largely based on innate immunity, and the etiologic agent is not transmitted after infection, and thus fungal evolution is not possible. Primary pathogens encompass two types, depending on their mode of transmission. Environmental pathogens have a double life cycle, and tend to become enzootic, adapted to a preferred host in a particular habitat. In contrast, pathogens that have a host-to-host transmission pattern are prone to shift to a neighboring, immunologically naive host, potentially leading to epidemics. Beyond these prototypical life cycles, some environmental fungi are able to make large leaps between dissimilar hosts/habitats, probably due to the similarity of key factors enabling survival in an entirely different niche, and thus allowing a change from opportunistic to primary pathogenicity. Mostly, such factors seem to be associated with extremotolerance.
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Affiliation(s)
- Sybren de Hoog
- RadboudUMC-CWZ Centre of Expertise for Mycology, 6525GA Nijmegen, The Netherlands
- Foundation Atlas of Clinical Fungi, 1214GP Hilversum, The Netherlands
- Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education of Guizhou & Key Laboratory of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Guizhou Medical University, 561113 Guiyang, China
- Postgraduate Program in Microbiology, Parasitology and Pathology, Biological Sciences, Department of Basic Pathology, Federal University of Paraná, 81531-980 Curitiba, Brazil
- Department of Medical Microbiology, Radboud University of Nijmegen, 6525AJ Nijmegen, The Netherlands
| | - Chao Tang
- RadboudUMC-CWZ Centre of Expertise for Mycology, 6525GA Nijmegen, The Netherlands
- Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education of Guizhou & Key Laboratory of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Guizhou Medical University, 561113 Guiyang, China
| | - Xin Zhou
- RadboudUMC-CWZ Centre of Expertise for Mycology, 6525GA Nijmegen, The Netherlands
- Third Affiliated Hospital of Sun Yat-sen University, 510630 Guangzhou, China
| | - Bruna Jacomel
- Postgraduate Program in Microbiology, Parasitology and Pathology, Biological Sciences, Department of Basic Pathology, Federal University of Paraná, 81531-980 Curitiba, Brazil
- Canisius Wilhelmina Hospital, 6532SZ Nijmegen, The Netherlands
| | - Bruno Lustosa
- RadboudUMC-CWZ Centre of Expertise for Mycology, 6525GA Nijmegen, The Netherlands
- Postgraduate Program in Engineering Bioprocess and Biotechnology, Department of Bioprocess Engineering and Biotechnology, Federal University of Paraná, 81531-980 Curitiba, Brazil
| | - Yinggai Song
- Department of Dermatology and Venerology, Peking University First Hospital,100034 Beijing, China
| | - Hazal Kandemir
- Westerdijk Fungal Biodiversity Center, 3584CT Utrecht, The Netherlands
| | - Sarah A Ahmed
- RadboudUMC-CWZ Centre of Expertise for Mycology, 6525GA Nijmegen, The Netherlands
- Foundation Atlas of Clinical Fungi, 1214GP Hilversum, The Netherlands
| | - Shaoqin Zhou
- RadboudUMC-CWZ Centre of Expertise for Mycology, 6525GA Nijmegen, The Netherlands
- Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education of Guizhou & Key Laboratory of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Guizhou Medical University, 561113 Guiyang, China
| | - Ricardo Belmonte-Lopes
- RadboudUMC-CWZ Centre of Expertise for Mycology, 6525GA Nijmegen, The Netherlands
- Postgraduate Program in Microbiology, Parasitology and Pathology, Biological Sciences, Department of Basic Pathology, Federal University of Paraná, 81531-980 Curitiba, Brazil
| | - Yu Quan
- RadboudUMC-CWZ Centre of Expertise for Mycology, 6525GA Nijmegen, The Netherlands
- Foundation Atlas of Clinical Fungi, 1214GP Hilversum, The Netherlands
| | - Peiying Feng
- Third Affiliated Hospital of Sun Yat-sen University, 510630 Guangzhou, China
| | - Vania A Vicente
- Postgraduate Program in Microbiology, Parasitology and Pathology, Biological Sciences, Department of Basic Pathology, Federal University of Paraná, 81531-980 Curitiba, Brazil
- Postgraduate Program in Engineering Bioprocess and Biotechnology, Department of Bioprocess Engineering and Biotechnology, Federal University of Paraná, 81531-980 Curitiba, Brazil
| | - Yingqian Kang
- Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education of Guizhou & Key Laboratory of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Guizhou Medical University, 561113 Guiyang, China
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Khadem S, Berry D, Al-Khlifeh E. Climate influences the gut eukaryome of wild rodents in the Great Rift Valley of Jordan. Parasit Vectors 2024; 17:358. [PMID: 39180136 PMCID: PMC11342738 DOI: 10.1186/s13071-024-06451-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 08/13/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND The mammalian gut microbiome includes a community of eukaryotes with significant taxonomic and functional diversity termed the eukaryome. The molecular analysis of eukaryotic diversity in microbiomes of wild mammals is still in its early stages due to the recent emergence of interest in this field. This study aimed to fill this knowledge gap by collecting data on eukaryotic species found in the intestines of wild rodents. Because little is known about the influence of climate on the gut eukaryome, we compared the composition of the gut eukaryotes in two rodent species, Mus musculus domesticus and Acomys cahirinus, which inhabit a transect crossing a temperate and tropical zone on the Jordanian side of the Great Rift Valley (GRV). METHODS We used high-throughput amplicon sequencing targeting the 18S rRNA gene in fecal samples from rodents to identify eukaryotic organisms, their relative abundance, and their potential for pathogenicity. RESULTS Nematodes and protozoa were the most prevalent species in the eukaryome communities, whereas fungi made up 6.5% of the total. Sixty percent of the eukaryotic ASVs belonged to taxa that included known pathogens. Eighty percent of the rodents were infected with pinworms, specifically Syphacia obvelata. Eukaryotic species diversity differed significantly between bioclimatic zones (p = 0.001). Nippostrongylus brasiliensis and Aspiculuris tetraptera were found to be present exclusively in the Sudanian zone rodents. This area has not reported any cases of Trichuris infections. Yet, Capillaria infestations were unique to the Mediterranean region, while Trichuris vulpis infestations were also prevalent in the Mediterranean and Irano-Turanian regions. CONCLUSIONS This study highlights the importance of considering host species diversity and environmental factors when studying eukaryome composition in wild mammals. These data will be valuable as a reference to eukaryome study.
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Affiliation(s)
- Sanaz Khadem
- Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, Division of Microbial Ecology, University of Vienna, Vienna, Austria
| | - David Berry
- Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, Division of Microbial Ecology, University of Vienna, Vienna, Austria
- Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna, Vienna, Austria
| | - Enas Al-Khlifeh
- Laboratory of Immunology, Department of Medical Laboratory Science, Al-Balqa Applied University, Al-Salt, Jordan.
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Wickramasinghe DN, Lyon CM, Lee S, Hepworth OW, Priest EL, Maufrais C, Ryan AP, Permal E, Sullivan D, McManus BA, Hube B, Butler G, d'Enfert C, Naglik JR, Richardson JP. Variations in candidalysin amino acid sequence influence toxicity and host responses. mBio 2024; 15:e0335123. [PMID: 38953356 PMCID: PMC11323794 DOI: 10.1128/mbio.03351-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Accepted: 06/10/2024] [Indexed: 07/04/2024] Open
Abstract
Candida albicans causes millions of mucosal infections in humans annually. Hyphal overgrowth on mucosal surfaces is frequently associated with tissue damage caused by candidalysin, a secreted peptide toxin that destabilizes the plasma membrane of host cells thereby promoting disease and immunopathology. Candidalysin was first identified in C. albicans strain SC5314, but recent investigations have revealed candidalysin "variants" of differing amino acid sequence in isolates of C. albicans, and the related species C. dubliniensis, and C tropicalis, suggesting that sequence variation among candidalysins may be widespread in natural populations of these Candida species. Here, we analyzed ECE1 gene sequences from 182 C. albicans isolates, 10 C. dubliniensis isolates, and 78 C. tropicalis isolates and identified 10, 3, and 2 candidalysin variants in these species, respectively. Application of candidalysin variants to epithelial cells revealed differences in the ability to cause cellular damage, changes in metabolic activity, calcium influx, MAPK signalling, and cytokine secretion, while biophysical analyses indicated that variants exhibited differences in their ability to interact with and permeabilize a membrane. This study identifies candidalysin variants with differences in biological activity that are present in medically relevant Candida species. IMPORTANCE Fungal infections are a significant burden to health. Candidalysin is a toxin produced by Candida albicans that damages host tissues, facilitating infection. Previously, we demonstrated that candidalysins exist in the related species C. dubliniensis and C. tropicalis, thereby identifying these molecules as a toxin family. Recent genomic analyses have highlighted the presence of a small number of candidalysin "variant" toxins, which have different amino acid sequences to those originally identified. Here, we screened genome sequences of isolates of C. albicans, C. dubliniensis, and C. tropicalis and identified candidalysin variants in all three species. When applied to epithelial cells, candidalysin variants differed in their ability to cause damage, activate intracellular signaling pathways, and induce innate immune responses, while biophysical analysis revealed differences in the ability of candidalysin variants to interact with lipid bilayers. These findings suggest that intraspecies variation in candidalysin amino acid sequence may influence fungal pathogenicity.
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Affiliation(s)
- Don N. Wickramasinghe
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, United Kingdom
| | - Claire M. Lyon
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, United Kingdom
| | - Sejeong Lee
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, United Kingdom
| | - Olivia W. Hepworth
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, United Kingdom
| | - Emily L. Priest
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, United Kingdom
| | - Corinne Maufrais
- Institut Pasteur, Université Paris Cité, INRAe USC 2019, Unité Biologie et Pathogénicité Fongiques, Paris, France
- Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, Paris, France
| | - Adam P. Ryan
- School of Biomedical and Biomolecular Science and UCD Conway Institute of Biomolecular and Biomedical Research, Conway Institute, University College Dublin, Dublin, Ireland
| | - Emmanuelle Permal
- Institut Pasteur, Université Paris Cité, INRAe USC 2019, Unité Biologie et Pathogénicité Fongiques, Paris, France
| | - Derek Sullivan
- Division of Oral Biosciences, Dublin Dental University Hospital, and School of Dental Science, Trinity College Dublin, Dublin, Ireland
| | - Brenda A. McManus
- Division of Oral Biosciences, Dublin Dental University Hospital, and School of Dental Science, Trinity College Dublin, Dublin, Ireland
| | - Bernhard Hube
- Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoll Institute (HKI), Jena, Germany
- Institute of Microbiology, Friedrich Schiller University, Jena, Germany
| | - Geraldine Butler
- School of Biomedical and Biomolecular Science and UCD Conway Institute of Biomolecular and Biomedical Research, Conway Institute, University College Dublin, Dublin, Ireland
| | - Christophe d'Enfert
- Institut Pasteur, Université Paris Cité, INRAe USC 2019, Unité Biologie et Pathogénicité Fongiques, Paris, France
| | - Julian R. Naglik
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, United Kingdom
| | - Jonathan P. Richardson
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, United Kingdom
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Muhmood A, Liu J, Liu D, Liu S, Azzam MM, Junaid MB, Hou L, Le G, Huang K. Mitigation of Deoxynivalenol (DON)- and Aflatoxin B1 (AFB1)-Induced Immune Dysfunction and Apoptosis in Mouse Spleen by Curcumin. Toxins (Basel) 2024; 16:356. [PMID: 39195766 PMCID: PMC11359138 DOI: 10.3390/toxins16080356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 08/04/2024] [Accepted: 08/06/2024] [Indexed: 08/29/2024] Open
Abstract
In the context of the potential immunomodulatory properties of curcumin in counteracting the detrimental effects of concurrent exposure to Deoxynivalenol (DON) and Aflatoxin B1 (AFB1), a comprehensive 28-days trial was conducted utilizing 60 randomly allocated mice divided into four groups. Administration of curcumin at a dosage of 5 mg/kg body weight in conjunction with DON at 0.1 mg/kg and AFB1 at 0.01 mg/kg body weight was undertaken to assess its efficacy. Results indicated that curcumin intervention demonstrated mitigation of splenic structural damage, augmentation of serum immunoglobulin A (IgA) and immunoglobulin G (IgG) levels, elevation in T lymphocyte subset levels, and enhancement in the mRNA expression levels of pro-inflammatory cytokines TNF-α, IFN-γ, IL-2, and IL-6. Furthermore, curcumin exhibited a suppressive effect on apoptosis in mice, as evidenced by decreased activity of caspase-3 and caspase-9, reduced expression levels of pro-apoptotic markers Bax and Cytochrome-c (Cyt-c) at both the protein and mRNA levels, and the maintenance of a balanced expression ratio of mitochondrial apoptotic regulators Bax and Bcl-2. Collectively, these findings offer novel insights into the therapeutic promise of curcumin in mitigating immunosuppression and apoptotic events triggered by mycotoxin co-exposure.
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Affiliation(s)
- Azhar Muhmood
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (A.M.); (J.L.); (D.L.); (S.L.); (L.H.); (G.L.)
- Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing 210095, China
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Jianxin Liu
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (A.M.); (J.L.); (D.L.); (S.L.); (L.H.); (G.L.)
- Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing 210095, China
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Dandan Liu
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (A.M.); (J.L.); (D.L.); (S.L.); (L.H.); (G.L.)
- Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing 210095, China
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Shuiping Liu
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (A.M.); (J.L.); (D.L.); (S.L.); (L.H.); (G.L.)
- Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing 210095, China
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Mahmoud M. Azzam
- Animal Production Department, College of Food and Agriculture Sciences, King Saud University, Riyadh 11451, Saudi Arabia;
| | - Muhammad Bilawal Junaid
- Department of Plant Production, College of Food and Agriculture Sciences, King Saud University, Riyadh 11451, Saudi Arabia;
| | - Lili Hou
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (A.M.); (J.L.); (D.L.); (S.L.); (L.H.); (G.L.)
- Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing 210095, China
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Guannan Le
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (A.M.); (J.L.); (D.L.); (S.L.); (L.H.); (G.L.)
- Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing 210095, China
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Kehe Huang
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; (A.M.); (J.L.); (D.L.); (S.L.); (L.H.); (G.L.)
- Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing 210095, China
- MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
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Yamari I, Abchir O, Nour H, Khedraoui M, Rossafi B, Errougui A, Talbi M, Samadi A, Kouali MHE, Chtita S. Unveiling Moroccan Nature's Arsenal: A Computational Molecular Docking, Density Functional Theory, and Molecular Dynamics Study of Natural Compounds against Drug-Resistant Fungal Infections. Pharmaceuticals (Basel) 2024; 17:886. [PMID: 39065737 PMCID: PMC11279552 DOI: 10.3390/ph17070886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 06/27/2024] [Accepted: 07/01/2024] [Indexed: 07/28/2024] Open
Abstract
Candida albicans and Aspergillus fumigatus are recognized as significant fungal pathogens, responsible for various human infections. The rapid emergence of drug-resistant strains among these fungi requires the identification and development of innovative antifungal therapies. We undertook a comprehensive screening of 297 naturally occurring compounds to address this challenge. Using computational docking techniques, we systematically analyzed the binding affinity of each compound to key proteins from Candida albicans (PDB ID: 1EAG) and Aspergillus fumigatus (PDB ID: 3DJE). This rigorous in silico examination aimed to unveil compounds that could potentially inhibit the activity of these fungal infections. This was followed by an ADMET analysis of the top-ranked compound, providing valuable insights into the pharmacokinetic properties and potential toxicological profiles. To further validate our findings, the molecular reactivity and stability were computed using the DFT calculation and molecular dynamics simulation, providing a deeper understanding of the stability and behavior of the top-ranking compounds in a biological environment. The outcomes of our study identified a subset of natural compounds that, based on our analysis, demonstrate notable potential as antifungal candidates. With further experimental validation, these compounds could pave the way for new therapeutic strategies against drug-resistant fungal pathogens.
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Affiliation(s)
- Imane Yamari
- Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Sidi Othman, Casablanca P.O. Box 7955, Morocco; (I.Y.); (O.A.); (M.K.); (B.R.); (A.E.); (M.T.); (M.E.K.)
| | - Oussama Abchir
- Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Sidi Othman, Casablanca P.O. Box 7955, Morocco; (I.Y.); (O.A.); (M.K.); (B.R.); (A.E.); (M.T.); (M.E.K.)
| | - Hassan Nour
- Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Sidi Othman, Casablanca P.O. Box 7955, Morocco; (I.Y.); (O.A.); (M.K.); (B.R.); (A.E.); (M.T.); (M.E.K.)
| | - Meriem Khedraoui
- Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Sidi Othman, Casablanca P.O. Box 7955, Morocco; (I.Y.); (O.A.); (M.K.); (B.R.); (A.E.); (M.T.); (M.E.K.)
| | - Bouchra Rossafi
- Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Sidi Othman, Casablanca P.O. Box 7955, Morocco; (I.Y.); (O.A.); (M.K.); (B.R.); (A.E.); (M.T.); (M.E.K.)
| | - Abdelkbir Errougui
- Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Sidi Othman, Casablanca P.O. Box 7955, Morocco; (I.Y.); (O.A.); (M.K.); (B.R.); (A.E.); (M.T.); (M.E.K.)
| | - Mohammed Talbi
- Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Sidi Othman, Casablanca P.O. Box 7955, Morocco; (I.Y.); (O.A.); (M.K.); (B.R.); (A.E.); (M.T.); (M.E.K.)
| | - Abdelouahid Samadi
- Department of Chemistry, College of Science, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
| | - MHammed El Kouali
- Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Sidi Othman, Casablanca P.O. Box 7955, Morocco; (I.Y.); (O.A.); (M.K.); (B.R.); (A.E.); (M.T.); (M.E.K.)
| | - Samir Chtita
- Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Sidi Othman, Casablanca P.O. Box 7955, Morocco; (I.Y.); (O.A.); (M.K.); (B.R.); (A.E.); (M.T.); (M.E.K.)
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Wattanasuntorn P, Phuektes P, Poapolathep S, Mimapan S, Tattiyapong M, Fink-Gremmels J, Oswald IP, Poapolathep A. Individual cytotoxicity of three major type A trichothecene, T-2, HT-2, and diacetoxyscirpenol in human Jurkat T cells. Toxicon 2024; 243:107718. [PMID: 38614246 DOI: 10.1016/j.toxicon.2024.107718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 03/21/2024] [Accepted: 04/10/2024] [Indexed: 04/15/2024]
Abstract
Mycotoxins are toxic, fungal secondary metabolites that contaminate agricultural commodities, food, and feed. Among them, T-2, HT-2, and diacetoxyscirpenol (DAS; the major type A trichothecene) are primarily produced from Fusarium species. These mycotoxins exert numerous toxicological effects in animals and humans, such as dermatotoxicity, haematotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity, and immunotoxicity. In the present study, human Jurkat T cells were used as a model to investigate apoptotic cell death induced by T-2, HT-2, and DAS. The results showed that T-2, HT-2, and DAS decreased cell viability and increased production of Reactive Oxygen Species in a time- and dose-dependency. Based on their IC50 values, they could be ranked in decreasing order of cytotoxicity as T-2 > HT-2 > DAS. All tested mycotoxins caused DNA fragmentation, up-regulated cytochrome C, caspase 3, and caspase 9 mRNA levels, and down-regulated the relative expression of Bcl-2 and caspase 8. The effects of these trichothecenes on apoptosis were determined based on flow cytometry. At the IC50 concentrations, the percentages of apoptotic cells were significantly higher than for the controls. Taken together, these data suggested that T-2, HT-2, and DAS could induce apoptosis through the mitochondrial apoptotic pathway.
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Affiliation(s)
- Phattarawadee Wattanasuntorn
- Interdisciplinary Graduate Program in Genetic Engineering, Graduate School, Kasetsart University, Bangkok, 10900, Thailand
| | - Patchara Phuektes
- Department of Pathobiology, Faculty of Veterinary Medicine, Khonkaen University, Khonkaen, 40002, Thailand
| | - Saranya Poapolathep
- Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, 10900, Thailand
| | - Sontana Mimapan
- National Institute of Animal Health (NIAH), Department of Livestock Development, Bangkok, 10900, Thailand
| | - Muncharee Tattiyapong
- National Institute of Animal Health (NIAH), Department of Livestock Development, Bangkok, 10900, Thailand
| | - Johanna Fink-Gremmels
- Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, the Netherlands
| | - Isabelle P Oswald
- Toxalim (Research Centre in Food Toxicology), Toulouse University, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Amnart Poapolathep
- Interdisciplinary Graduate Program in Genetic Engineering, Graduate School, Kasetsart University, Bangkok, 10900, Thailand; Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, 10900, Thailand.
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Abraham E, Athapaththu AMGK, Atanasova KR, Chen QY, Corcoran TJ, Piloto J, Wu CW, Ratnayake R, Luesch H, Choe KP. Chemical Genetics in C. elegans Identifies Anticancer Mycotoxins Chaetocin and Chetomin as Potent Inducers of a Nuclear Metal Homeostasis Response. ACS Chem Biol 2024; 19:1180-1193. [PMID: 38652683 PMCID: PMC11102292 DOI: 10.1021/acschembio.4c00131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2024]
Abstract
C. elegans numr-1/2 (nuclear-localized metal-responsive) is an identical gene pair encoding a nuclear protein previously shown to be activated by cadmium and disruption of the integrator RNA metabolism complex. We took a chemical genetic approach to further characterize regulation of this novel metal response by screening 41,716 compounds and extracts for numr-1p::GFP activation. The most potent activator was chaetocin, a fungal 3,6-epidithiodiketopiperazine (ETP) with promising anticancer activity. Chaetocin activates numr-1/2 strongly in the alimentary canal but is distinct from metal exposure, because it represses canonical cadmium-responsive metallothionine genes. Chaetocin has diverse targets in cancer cells including thioredoxin reductase, histone lysine methyltransferase, and acetyltransferase p300/CBP; further work is needed to identify the mechanism in C. elegans as genetic disruption and RNAi screening of homologues did not induce numr-1/2 in the alimentary canal and chaetocin did not affect markers of integrator dysfunction. We demonstrate that disulfides in chaetocin and chetomin, a dimeric ETP analog, are required to induce numr-1/2. ETP monomer gliotoxin, despite possessing a disulfide linkage, had almost no effect on numr-1/2, suggesting a dimer requirement. Chetomin inhibits C. elegans growth at low micromolar levels, and loss of numr-1/2 increases sensitivity; C. elegans and Chaetomiaceae fungi inhabit similar environments raising the possibility that numr-1/2 functions as a defense mechanism. There is no direct orthologue of numr-1/2 in humans, but RNaseq suggests that chaetocin affects expression of cellular processes linked to stress response and metal homeostasis in colorectal cancer cells. Our results reveal interactions between metal response gene regulation and ETPs and identify a potential mechanism of resistance to this versatile class of preclinical compounds.
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Affiliation(s)
- Elijah Abraham
- Department of Biology, University of Florida, Gainesville, FL 32611, USA
| | | | - Kalina R. Atanasova
- Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, United States
- Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, Florida 32610, United States
| | - Qi-Yin Chen
- Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, United States
- Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, Florida 32610, United States
| | - Taylor J. Corcoran
- Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, United States
- Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, Florida 32610, United States
| | - Juan Piloto
- Department of Biology, University of Florida, Gainesville, FL 32611, USA
| | - Cheng-Wei Wu
- Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, S&N 5B4 Canada
| | - Ranjala Ratnayake
- Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, United States
- Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, Florida 32610, United States
| | - Hendrik Luesch
- Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, United States
- Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, Florida 32610, United States
| | - Keith P. Choe
- Department of Biology, University of Florida, Gainesville, FL 32611, USA
- Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, Florida 32610, United States
- Genetics Institute, University of Florida, Gainesville, FL 32610, USA
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Singh V, Mandal P, Chauhan SS, Saifi IJ, Marhaba, Sandeep PV, Jagdale P, Ayanur A, Ansari KM. Chronic exposure to Zearalenone leads to endometrial hyperplasia in CD-1 mice by altering the inflammatory markers. Toxicol Res (Camb) 2024; 13:tfae055. [PMID: 38645625 PMCID: PMC11031408 DOI: 10.1093/toxres/tfae055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 03/14/2024] [Accepted: 04/02/2024] [Indexed: 04/23/2024] Open
Abstract
Background Zearalenone (ZEA), a natural food contaminant, is reported to act as a mycoestrogen due to its estrogen-mimicking properties. According to studies, ZEA has a greater potential for estrogenic activity compared to any other naturally occurring non-steroidal estrogen. ZEA has been found in the endometrium of individuals with reproductive problems and the serum of children facing early puberty. These studies suggested a possible link between ZEA exposure and endometrial toxicity; nonetheless, no thorough research has been done. This study assessed the endometrium's response to chronic ZEA exposure. Methods Four groups of CD-1 female mice were exposed to control, estradiol (E2), and two different doses of ZEA for 90 days. At the end of treatment, blood and uterus were collected, and samples were used for inflammatory cytokines level, immunochemical, histopathological, and biophysical analysis. Results Our data indicated that the uterus showed a change in body/organ weight ratio, while other organs did not have any notable changes. Immunochemical and histological studies showed hyperplasia and a higher number of glands in the endometrium after ZEA and E2 exposure. Similarly, proliferation markers such as proliferative cell nuclear antigen (PCNA), Ki-67, and inflammatory cytokines such as interleukin 6 (IL-6), interleukin 8 (IL-8), and interferon-gamma (IFN-?) levels were found to be higher in the E2 and ZEA-exposed groups. Conclusion Our finding conclude that ZEA targets the uterus and cause inflammation due to increased levels of inflammatory cytokines and proliferation mediators, as well as systemic toxicity denoted by a strong binding affinity with serum proteins.
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Affiliation(s)
- Varsha Singh
- Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR) Kamla Nehru Nagar, Ghaziabad, 201002, Uttar Pradesh, India
| | - Payal Mandal
- Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India
| | - Shweta Singh Chauhan
- Academy of Scientific and Innovative Research (AcSIR) Kamla Nehru Nagar, Ghaziabad, 201002, Uttar Pradesh, India
- Computational Toxicology Facility, Toxicoinformatics and Industrial Research, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India
| | - Ishrat Jahan Saifi
- Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR) Kamla Nehru Nagar, Ghaziabad, 201002, Uttar Pradesh, India
| | - Marhaba
- Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR) Kamla Nehru Nagar, Ghaziabad, 201002, Uttar Pradesh, India
| | - P V Sandeep
- Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India
| | - Pankaj Jagdale
- Central Pathology Facility, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India
| | - Anjaneya Ayanur
- Central Pathology Facility, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India
| | - Kausar Mahmood Ansari
- Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR) Kamla Nehru Nagar, Ghaziabad, 201002, Uttar Pradesh, India
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de Sales-Neto JM, Rodrigues-Mascarenhas S. Immunosuppressive effects of the mycotoxin patulin in macrophages. Arch Microbiol 2024; 206:166. [PMID: 38485821 DOI: 10.1007/s00203-024-03928-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/04/2024] [Accepted: 03/08/2024] [Indexed: 03/19/2024]
Abstract
Patulin (PAT) is a fungi-derived secondary metabolite produced by numerous fungal species, especially within Aspergillus, Byssochlamys, and Penicillium genera, amongst which P. expansum is the foremost producer. Similar to other fungi-derived metabolites, PAT has been shown to have diverse biological features. Initially, PAT was used as an effective antimicrobial agent against Gram-negative and Gram-positive bacteria. Then, PAT has been shown to possess immunosuppressive properties encompassing humoral and cellular immune response, immune cell function and activation, phagocytosis, nitric oxide and reactive oxygen species production, cytokine release, and nuclear factor-κB and mitogen-activated protein kinases activation. Macrophages are a heterogeneous population of immune cells widely distributed throughout organs and connective tissue. The chief function of macrophages is to engulf and destroy foreign bodies through phagocytosis; this ability was fundamental to his discovery. However, macrophages play other well-established roles in immunity. Thus, considering the central role of macrophages in the immune response, we review the immunosuppressive effects of PAT in macrophages and provide the possible mechanisms of action.
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Affiliation(s)
- José Marreiro de Sales-Neto
- Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraíba, João Pessoa, CEP: 58051-900, PB, BR, Brazil
| | - Sandra Rodrigues-Mascarenhas
- Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraíba, João Pessoa, CEP: 58051-900, PB, BR, Brazil.
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Parak M, Asgari A, Hasani Nourian Y, Ghanei M. A review of poisoning with various types of biotoxins and its common clinical symptoms. Toxicon 2024; 240:107629. [PMID: 38336277 DOI: 10.1016/j.toxicon.2024.107629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Revised: 01/01/2024] [Accepted: 01/23/2024] [Indexed: 02/12/2024]
Abstract
INTRODUCTION Biotoxins are toxic substances that originate from living organisms and are harmful to humans. Therefore, we need to know the symptoms of biotoxins poisoning to manage the damage. The purpose of this study is to establish a practical diagnostic protocol for dealing with poisoned patients exposed to biotoxins. MATERIALS AND METHODS The present study is a review study. Our studied community is articles and books matching the title of the project and relevant keywords. First, by searching the key words sign, symptom, biotoxins, relevant articles were extracted and studied from valid databases. By reviewing the studies based on the search strategy, four groups of biotoxins that were studied the most were identified. These four groups are marine biotoxins, bacterial biotoxins, fungal biotoxins and plant biotoxins. In each of these biotoxin groups, important toxins were selected and studied. RESULTS A total of 1864 articles were initially identified from the databases searched in present study. After screening titles and abstracts, 26 articles were included in the systematic review. Specifically, 7 articles were included for bacterial toxins, 9 articles for marine toxins, 5 articles for plant toxins and 5 articles for fungal toxins. CONCLUSION The symptoms of plant biotoxins poisoning may include cardiovascular, hematologic, neurologic, respiratory, renal, and gastrointestinal symptoms, while the symptoms of fungal biotoxins poisoning may include hepatic, renal, gastrointestinal, musculoskeletal, metabolic, respiratory, neurological, and cardiovascular symptoms. marine biotoxins poisoning presents with gastrointestinal and neurological symptoms, with varying incubation periods and recovery times. bacterial biotoxins exposure can lead to a wide range of clinical symptoms, with diarrhea, vomiting, and abdominal pain being the most common, and hemoglobinuria or hematuria being a sensitive and specific clinical manifestation for diagnosing ongoing HUS in children.
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Affiliation(s)
- Mohammadreza Parak
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Alireza Asgari
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Yazdan Hasani Nourian
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Mostafa Ghanei
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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17
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Ayeni K, Seki D, Pjevac P, Hausmann B, Krausová M, Braun D, Wisgrill L, Berry D, Warth B, Ezekiel CN. Biomonitoring of Dietary Mycotoxin Exposure and Associated Impact on the Gut Microbiome in Nigerian Infants. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58:2236-2246. [PMID: 38252460 PMCID: PMC10851434 DOI: 10.1021/acs.est.3c07786] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 01/06/2024] [Accepted: 01/09/2024] [Indexed: 01/23/2024]
Abstract
Mycotoxins are toxic chemicals that adversely affect human health. Here, we assessed the influence of mycotoxin exposure on the longitudinal development of early life intestinal microbiota of Nigerian neonates and infants (NIs). Human biomonitoring assays based on liquid chromatography tandem mass spectrometry were applied to quantify mycotoxins in breast milk (n = 68) consumed by the NIs, their stool (n = 82), and urine samples (n = 15), which were collected longitudinally from month 1-18 postdelivery. Microbial community composition was characterized by 16S rRNA gene amplicon sequencing of stool samples and was correlated to mycotoxin exposure patterns. Fumonisin B1 (FB1), FB2, and alternariol monomethyl ether (AME) were frequently quantified in stool samples between months 6 and 18. Aflatoxin M1 (AFM1), AME, and citrinin were quantified in breast milk samples at low concentrations. AFM1, FB1, and ochratoxin A were quantified in urine samples at relatively high concentrations. Klebsiella and Escherichia/Shigella were dominant in very early life stool samples (month 1), whereas Bifidobacterium was dominant between months 3 and 6. The total mycotoxin levels in stool were significantly associated with NIs' gut microbiome composition (PERMANOVA, p < 0.05). However, no significant correlation was observed between specific microbiota and the detection of certain mycotoxins. Albeit a small cohort, this study demonstrates that mycotoxins may influence early life gut microbiome composition.
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Affiliation(s)
- Kolawole
I. Ayeni
- Department
of Microbiology, Babcock University, Ilishan Remo PMB 4003, Ogun State, Nigeria
- University
of Vienna, Faculty of Chemistry, Department of Food Chemistry and
Toxicology, Währinger
Straße 38, Vienna 1090, Austria
| | - David Seki
- Joint
Microbiome Facility of the Medical University of Vienna and the University
of Vienna, Djerassiplatz 1, Vienna 1030, Austria
- Division
of Clinical Microbiology, Department of Laboratory Medicine, Medical University of Vienna, Vienna 1090, Austria
| | - Petra Pjevac
- Joint
Microbiome Facility of the Medical University of Vienna and the University
of Vienna, Djerassiplatz 1, Vienna 1030, Austria
- Department
of Microbiology and Ecosystem Science, Centre for Microbiology and
Environmental Systems Science, University
of Vienna, Djerassiplatz
1, Vienna 1030, Austria
| | - Bela Hausmann
- Joint
Microbiome Facility of the Medical University of Vienna and the University
of Vienna, Djerassiplatz 1, Vienna 1030, Austria
- Division
of Clinical Microbiology, Department of Laboratory Medicine, Medical University of Vienna, Vienna 1090, Austria
| | - Magdaléna Krausová
- University
of Vienna, Faculty of Chemistry, Department of Food Chemistry and
Toxicology, Währinger
Straße 38, Vienna 1090, Austria
| | - Dominik Braun
- University
of Vienna, Faculty of Chemistry, Department of Food Chemistry and
Toxicology, Währinger
Straße 38, Vienna 1090, Austria
| | - Lukas Wisgrill
- Division
of Neonatology, Pediatric Intensive Care and Neuropediatrics, Comprehensive
Center for Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna 1090, Austria
- Exposome
Austria, Research Infrastructure and National EIRENE Node, Vienna 1090, Austria
| | - David Berry
- Joint
Microbiome Facility of the Medical University of Vienna and the University
of Vienna, Djerassiplatz 1, Vienna 1030, Austria
- Department
of Microbiology and Ecosystem Science, Centre for Microbiology and
Environmental Systems Science, University
of Vienna, Djerassiplatz
1, Vienna 1030, Austria
| | - Benedikt Warth
- University
of Vienna, Faculty of Chemistry, Department of Food Chemistry and
Toxicology, Währinger
Straße 38, Vienna 1090, Austria
- Exposome
Austria, Research Infrastructure and National EIRENE Node, Vienna 1090, Austria
| | - Chibundu N. Ezekiel
- Department
of Microbiology, Babcock University, Ilishan Remo PMB 4003, Ogun State, Nigeria
- University
of Natural Resources and Life Sciences Vienna (BOKU), Department of
Agrobiotechnology (IFA-Tulln), Institute for Bioanalytics and Agro-Metabolomics, Konrad-LorenzStr. 20, Tulln 3430, Austria
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18
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Zhao N, Zhu M, Liu Q, Shen Y, Duan S, Zhu L, Yang J. AoPrdx2 Regulates Oxidative Stress, Reactive Oxygen Species, Trap Formation, and Secondary Metabolism in Arthrobotrys oligospora. J Fungi (Basel) 2024; 10:110. [PMID: 38392782 PMCID: PMC10890406 DOI: 10.3390/jof10020110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/23/2024] [Accepted: 01/25/2024] [Indexed: 02/24/2024] Open
Abstract
Prdx2 is a peroxiredoxin (Prx) family protein that protects cells from attack via reactive oxygen species (ROS), and it has an important role in improving the resistance and scavenging capacity of ROS in fungi. Arthrobotrys oligospora is a widespread nematode-trapping fungus that can produce three-dimensional nets to capture and kill nematodes. In this study, AoPrdx2, a homologous protein of Prx5, was investigated in A. oligospora via gene disruption, phenotypic analysis, and metabolomics. The deletion of Aoprdx2 resulted in an increase in the number of mycelial septa and a reduction in the number of nuclei and spore yield. Meanwhile, the absence of Aoprdx2 increased sensitivity to oxidative stresses, whereas the ∆Aoprdx2 mutant strain resulted in higher ROS levels than that of the wild-type (WT) strain. In particular, the inactivation of Aoprdx2 severely influenced trap formation and pathogenicity; the number of traps produced by the ∆Aoprdx2 mutant strain was remarkably reduced and the number of mycelial rings of traps in the ∆Aoprdx2 mutant strain was less than that of the WT strain. In addition, the abundance of metabolites in the ∆Aoprdx2 mutant strain was significantly downregulated compared with the WT strain. These results indicate that AoPrdx2 plays an indispensable role in the scavenging of ROS, trap morphogenesis, and secondary metabolism.
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Affiliation(s)
- Na Zhao
- State Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, China
| | - Meichen Zhu
- State Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, China
| | - Qianqian Liu
- State Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, China
| | - Yanmei Shen
- State Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, China
| | - Shipeng Duan
- State Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, China
| | - Lirong Zhu
- State Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, China
| | - Jinkui Yang
- State Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, China
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Shandilya UK, Sharma A, Xu R, Muniz MMM, Karrow NA. Evaluation of Immunomodulatory Effects of Fusarium Mycotoxins Using Bacterial Endotoxin-Stimulated Bovine Epithelial Cells and Macrophages in Co-Culture. Genes (Basel) 2023; 14:2014. [PMID: 38002956 PMCID: PMC10671659 DOI: 10.3390/genes14112014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 10/20/2023] [Accepted: 10/26/2023] [Indexed: 11/26/2023] Open
Abstract
Mycotoxins are secondary metabolites produced by a variety of fungi that contaminate animal food and feeds and are capable of inducing a wide range of toxicities. Predictive in vitro models represent valuable substitutes for animal experiments to assess the toxicity of mycotoxins. The complexities of the interactions between epithelial and innate immune cells, vital for upholding barrier integrity and averting infections, remain inadequately understood. In the current study, a co-culture model of bovine epithelial cells (MAC-T) and macrophages (BoMac) was used to investigate the impact of exposure to Fusarium mycotoxins, namely deoxynivalenol (DON), zearalenone (ZEN), enniatin B (ENB), and beauvericin (BEA), on the inflammatory response elicited by the bacterial lipopolysaccharide (LPS) endotoxin. The MAC-T cells and BoMac were seeded on the apical side of a Transwell membrane and in the lower chamber, respectively, and mycotoxin exposure on the apical side of the membrane was carried out with the different mycotoxins (LC20; concentrations that elicited 20% cytotoxicity) for 48 h followed by an LPS immunity challenge for 24 h. The culture supernatants were collected from the basolateral compartment and these samples were submitted for cytokine/chemokine multiplex analysis. RNA-Seq analysis was performed using total RNA extracted from the MAC-T cells to acquire a more detailed insight into their cellular functions. The multiplex analysis indicated that IFN-γ, IL-1α, IL-8, and MCP-1 were significantly induced post-DON treatment when compared to control cells, and levels of IL-1α and IL-8 were enhanced significantly in all mycotoxin-treated groups post-LPS challenge. Analysis of the sequencing results showed that there were 341, 357, and 318 differentially expressed MAC-T cell genes that were up-regulated in the DON, ENB, and BEA groups, respectively. Gene ontology and pathway analysis revealed that these DEGs were significantly enriched in various biological processes and pathways related to inflammation, apoptosis signaling, and Wnt signaling. These results provide a comprehensive analysis of the co-culture cytokine/chemokine production and MAC-T cells' gene expression profiles elicited by Fusarium mycotoxins, which further contributes to the understanding of early endotoxemia post-mycotoxin exposure.
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Affiliation(s)
| | | | | | | | - Niel A. Karrow
- Department of Animal Biosciences, University of Guelph, 50 Stone Rd. E., Guelph, ON N1G2W1, Canada; (U.K.S.); (A.S.); (R.X.); (M.M.M.M.)
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20
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Hosseini S, Brenig B, Winitchakorn S, Kanmanee C, Srinual O, Tapingkae W, Gatphayak K. Genetic assessment of the effect of red yeast ( Sporidiobolus pararoseus) as a feed additive on mycotoxin toxicity in laying hens. Front Microbiol 2023; 14:1254569. [PMID: 37744913 PMCID: PMC10512063 DOI: 10.3389/fmicb.2023.1254569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 08/21/2023] [Indexed: 09/26/2023] Open
Abstract
Toxic fungal species produce hazardous substances known as mycotoxins. Consumption of mycotoxin contaminated feed and food causes a variety of dangerous diseases and can even lead to death of animals and humans, raising global concerns for adverse health effects. To date, several strategies have been developed to counteract with mycotoxin contamination. Red yeast as a novel biological dietary agent is a promising strategy to eliminate mycotoxicity in living organisms. Poultry are most susceptible animals to mycotoxin contamination, as they are fed a mixture of grains and are at higher risk of co-exposure to multiple toxic fungal substances. Therefore, this study investigated the genetic mechanism underlying long-term feeding with red yeast supplementation in interaction with multiple mycotoxins using transcriptome profiling (RNA_Seq) in the liver of laying hens. The results showed a high number of significantly differentially expressed genes in liver of chicken fed with a diet contaminated with mycotoxins, whereas the number of Significantly expressed genes was considerably reduced when the diet was supplemented with red yeast. The expression of genes involved in the phase I (CYP1A1, CYP1A2) and phase II (GSTA2, GSTA3, MGST1) detoxification process was downregulated in animals fed with mycotoxins contaminated diet, indicating suppression of the detoxification mechanisms. However, genes involved in antioxidant defense (GSTO1), apoptosis process (DUSP8), and tumor suppressor (KIAA1324, FBXO47, NME6) were upregulated in mycotoxins-exposed animals, suggesting activation of the antioxidant defense in response to mycotoxicity. Similarly, none of the detoxification genes were upregulated in hens fed with red yeast supplemented diet. However, neither genes involved in antioxidant defense nor tumor suppressor genes were expressed in the animals exposed to the red yeast supplemented feed, suggesting decreases the adsorption of biologically active mycotoxins in the liver of laying hens. We conclude that red yeast can act as a mycotoxin binder to decrease the adsorption of mycotoxins in the liver of laying hens and can be used as an effective strategy in the poultry feed industry to eliminate the adverse effects of mycotoxins for animals and increase food safety for human consumers.
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Affiliation(s)
- Shahrbanou Hosseini
- Molecular Biology of Livestock and Molecular Diagnostics, Department of Animal Sciences, University of Goettingen, Göttingen, Germany
- Institute of Veterinary Medicine, University of Goettingen, Göttingen, Germany
| | - Bertram Brenig
- Molecular Biology of Livestock and Molecular Diagnostics, Department of Animal Sciences, University of Goettingen, Göttingen, Germany
- Institute of Veterinary Medicine, University of Goettingen, Göttingen, Germany
| | | | - Chanidapha Kanmanee
- Department of Animal and Aquatic Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Orranee Srinual
- Department of Animal and Aquatic Sciences, Chiang Mai University, Chiang Mai, Thailand
- Functional Feed Innovation Center, Faculty of Agriculture, Chiang Mai University, Chiang Mai, Thailand
| | - Wanaporn Tapingkae
- Department of Animal and Aquatic Sciences, Chiang Mai University, Chiang Mai, Thailand
- Functional Feed Innovation Center, Faculty of Agriculture, Chiang Mai University, Chiang Mai, Thailand
| | - Kesinee Gatphayak
- Department of Animal and Aquatic Sciences, Chiang Mai University, Chiang Mai, Thailand
- Functional Feed Innovation Center, Faculty of Agriculture, Chiang Mai University, Chiang Mai, Thailand
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21
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Huang S, Zhao X, Luo Z, Tang X, Zhou Y, Keyhani N, Zhang Y. Fungal co-expression network analyses identify pathogen gene modules associated with host insect invasion. Microbiol Spectr 2023; 11:e0180923. [PMID: 37656157 PMCID: PMC10581046 DOI: 10.1128/spectrum.01809-23] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 07/06/2023] [Indexed: 09/02/2023] Open
Abstract
The broad host range fungal insect pathogen, Beauveria bassiana, has been commercialized as an alternative to chemical insecticides for pest control worldwide. B. bassiana represents a unique model system with which to examine host-pathogen interactions, and a wide range of genes and processes have been studied. However, significant aspects of virulence, particularly on the genomic scale, remain poorly studied. Here, we have combined available transcriptomes with three newly generated data sets for a combined total analysis of 76 deep-sequenced samples covering growth, development, stress responses, and infection during the life cycle of B. bassiana. Co-expression network analyses resulted in the identification of gene modules enriched during two critical stages of the infection process, namely (i) cuticle penetration and (ii) in vivo hyphal body (dimorphic transition) growth capable of avoiding innate and humoral immune defenses. These analyses identify unique signatures of metabolism, signaling, secondary metabolite production, host defense suppression, membrane reorganization, effector production, and secretion for each stage, including genetic regulators and epigenetic patterns. These data provide a comprehensive framework for understanding and probing fungal adaptations to its pathogenic life cycle and expand the candidate repertoire for continued dissection of the host-pathogen interaction. IMPORTANCE Insect fungal pathogens have evolved unique strategies for overcoming host structural and immunological defenses that span from the sclerotized cuticle to innate and humoral cellular responses. Two critical stages of the infection process involve (i) cuticle penetration and (ii) immune evasion within the insect hemocoel. A set of 76 global transcriptomic data for B. bassiana that include the cuticle penetration and hemocoel growth stages were analyzed for patterns (gene modules) of expression, yielding unique insights into these different life stages. These analyses integrate gene networks involved in fungal development, stress response and pathogenesis to further the systematic understanding of the global processes integral to the unique adaptation employed by fungal pathogens of insects.
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Affiliation(s)
- Shuaishuai Huang
- Key Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Plant Protection, Southwest University, Chongqing, China
- Key Laboratory of Biodiversity and Environment on the Qinghai-Tibet Plateau (Ministry of Education), School of Ecology and Environment, Tibet University, Tibet, China
| | - Xin Zhao
- Key Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Plant Protection, Southwest University, Chongqing, China
| | - Zhibing Luo
- Key Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Plant Protection, Southwest University, Chongqing, China
| | - Xiaohan Tang
- Key Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Plant Protection, Southwest University, Chongqing, China
| | - Yonghong Zhou
- Key Laboratory of Biodiversity and Environment on the Qinghai-Tibet Plateau (Ministry of Education), School of Ecology and Environment, Tibet University, Tibet, China
| | - Nemat Keyhani
- Department of Biological Sciences, University of Illinois, Chicago, Illinois, USA
| | - Yongjun Zhang
- Key Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Plant Protection, Southwest University, Chongqing, China
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22
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Zhgun AA. Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle. Int J Mol Sci 2023; 24:11184. [PMID: 37446362 PMCID: PMC10342363 DOI: 10.3390/ijms241311184] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 06/28/2023] [Accepted: 07/03/2023] [Indexed: 07/15/2023] Open
Abstract
Filamentous fungi are one of the most important producers of secondary metabolites. Some of them can have a toxic effect on the human body, leading to diseases. On the other hand, they are widely used as pharmaceutically significant drugs, such as antibiotics, statins, and immunosuppressants. A single fungus species in response to various signals can produce 100 or more secondary metabolites. Such signaling is possible due to the coordinated regulation of several dozen biosynthetic gene clusters (BGCs), which are mosaically localized in different regions of fungal chromosomes. Their regulation includes several levels, from pathway-specific regulators, whose genes are localized inside BGCs, to global regulators of the cell (taking into account changes in pH, carbon consumption, etc.) and global regulators of secondary metabolism (affecting epigenetic changes driven by velvet family proteins, LaeA, etc.). In addition, various low-molecular-weight substances can have a mediating effect on such regulatory processes. This review is devoted to a critical analysis of the available data on the "turning on" and "off" of the biosynthesis of secondary metabolites in response to signals in filamentous fungi. To describe the ongoing processes, the model of "piano regulation" is proposed, whereby pressing a certain key (signal) leads to the extraction of a certain sound from the "musical instrument of the fungus cell", which is expressed in the production of a specific secondary metabolite.
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Affiliation(s)
- Alexander A Zhgun
- Group of Fungal Genetic Engineering, Federal Research Center "Fundamentals of Biotechnology", Russian Academy of Sciences, Leninsky Prosp. 33-2, 119071 Moscow, Russia
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Nowak A, Kutyła M, Kaczmarek J, Jaroszuk-Ściseł J, Jędryczka M. Differences in the Production of Extracellular Polymeric Substances (EPS) and Other Metabolites of Plenodomus ( Leptosphaeria) Infecting Winter Oilseed Rape ( Brassica napus L.). Metabolites 2023; 13:759. [PMID: 37367918 DOI: 10.3390/metabo13060759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 06/12/2023] [Accepted: 06/14/2023] [Indexed: 06/28/2023] Open
Abstract
Species of the genus Plenodomus (Leptosphaeria) are phytopathogens of the Brassicaceae family, which includes oilseed rape. The spores of these fungi spread by airborne transmission, infect plants, and cause crop losses. The secondary metabolism of P. lingam and P. biglobosus was studied and compared, with the main focus being on the ability to produce Extracellular Polymeric Substances (EPS). In spite of the 1.5-2-fold faster growth rate of P. biglobosus on Czapek-Dox and other screening media, the average yield of EPS in this fungus was only 0.29 g/L, compared to that of P. lingam (0.43 g/L). In turn, P. biglobosus showed a higher capacity to synthesise IAA, i.e., 14 µg/mL, in contrast to <1.5 µg/mL produced by P. lingam. On the other hand, the P. lingam strains showed higher β-glucanase activity (350-400 mU/mL), compared to 50-100 mU/mL in P. biglobosus. Invertase levels were similar in both species (250 mU/mL). The positive correlation between invertase activity and EPS yield contrasted with the absence of a correlation of EPS with β-glucanase. Plenodomus neither solubilised phosphate nor used proteins from milk. All strains showed the ability to synthesise siderophores on CAS agar. P. biglobosus exhibited the highest efficiency of amylolytic and cellulolytic activity.
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Affiliation(s)
- Artur Nowak
- Department of Industrial and Environmental Microbiology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
| | - Mateusz Kutyła
- Department of Industrial and Environmental Microbiology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
| | - Joanna Kaczmarek
- Department of Pathogen Genetics and Plant Resistance, Institute of Plant Genetics, Polish Academy of Sciences, Strzeszyńska 34, 60-479 Poznań, Poland
| | - Jolanta Jaroszuk-Ściseł
- Department of Industrial and Environmental Microbiology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
| | - Małgorzata Jędryczka
- Department of Pathogen Genetics and Plant Resistance, Institute of Plant Genetics, Polish Academy of Sciences, Strzeszyńska 34, 60-479 Poznań, Poland
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Corbu VM, Gheorghe-Barbu I, Dumbravă AȘ, Vrâncianu CO, Șesan TE. Current Insights in Fungal Importance-A Comprehensive Review. Microorganisms 2023; 11:1384. [PMID: 37374886 DOI: 10.3390/microorganisms11061384] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 05/20/2023] [Accepted: 05/22/2023] [Indexed: 06/29/2023] Open
Abstract
Besides plants and animals, the Fungi kingdom describes several species characterized by various forms and applications. They can be found in all habitats and play an essential role in the excellent functioning of the ecosystem, for example, as decomposers of plant material for the cycling of carbon and nutrients or as symbionts of plants. Furthermore, fungi have been used in many sectors for centuries, from producing food, beverages, and medications. Recently, they have gained significant recognition for protecting the environment, agriculture, and several industrial applications. The current article intends to review the beneficial roles of fungi used for a vast range of applications, such as the production of several enzymes and pigments, applications regarding food and pharmaceutical industries, the environment, and research domains, as well as the negative impacts of fungi (secondary metabolites production, etiological agents of diseases in plants, animals, and humans, as well as deteriogenic agents).
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Affiliation(s)
- Viorica Maria Corbu
- Genetics Department, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
- Research Institute of the University of Bucharest-ICUB, 91-95 Spl. Independentei, 050095 Bucharest, Romania
| | - Irina Gheorghe-Barbu
- Research Institute of the University of Bucharest-ICUB, 91-95 Spl. Independentei, 050095 Bucharest, Romania
- Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
| | - Andreea Ștefania Dumbravă
- Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
| | - Corneliu Ovidiu Vrâncianu
- Research Institute of the University of Bucharest-ICUB, 91-95 Spl. Independentei, 050095 Bucharest, Romania
- Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
| | - Tatiana Eugenia Șesan
- Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest, 060101 Bucharest, Romania
- Academy of Agricultural Sciences and Forestry, 61 Bd. Mărăşti, District 1, 011464 Bucharest, Romania
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25
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Sajid M, Srivastava S, Yadav RK, Joshi L, Bharadwaj M. Fungal Community Composition and Function Associated with Loose Smokeless Tobacco Products. Curr Microbiol 2023; 80:131. [PMID: 36894760 DOI: 10.1007/s00284-023-03237-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 02/20/2023] [Indexed: 03/11/2023]
Abstract
Smokeless tobacco products (STPs) contain several microbial communities which are responsible for the formation of carcinogens, like tobacco-specific nitrosamine (TSNAs). A majority of STPs are sold in loose/unpackaged form which can be loaded with a diverse microbial population. Here, the fungal population and mycotoxins level of three popular Indian loose STPs, Dohra, Mainpuri Kapoori (MK), and loose leaf-chewing tobacco (LCT) was examined using metagenomic sequencing of ITS1 DNA segment of the fungal genome and LC-MS/MS, respectively. We observed that Ascomycota was the most abundant phylum and Sterigmatomyces and Pichia were the predominant fungal genera in loose STPs. MK displayed the highest α-diversity being enriched with pathogenic fungi Apiotrichum, Aspergillus, Candida, Fusarium, Trichosporon, and Wallemia. Further, FUNGuild analysis revealed an abundance of saprotrophs in MK, while pathogen-saprotroph-symbiotroph were abundant in Dohra and LCT. The level of a fungal toxin (ochratoxins A) was high in the MK product. This study caution that loose STPs harbor various harmful fungi that can infect their users and deliver fungal toxins or disrupt the oral microbiome of SLT users which can contribute to several oral pathologies.
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Affiliation(s)
- Mohammad Sajid
- Division of Molecular Genetics and Biochemistry, Molecular Biology Group, ICMR-National Institute of Cancer Prevention and Research, Noida, Uttar Pradesh, India
| | - Sonal Srivastava
- Division of Molecular Genetics and Biochemistry, Molecular Biology Group, ICMR-National Institute of Cancer Prevention and Research, Noida, Uttar Pradesh, India
| | - Ravi K Yadav
- Division of Molecular Genetics and Biochemistry, Molecular Biology Group, ICMR-National Institute of Cancer Prevention and Research, Noida, Uttar Pradesh, India
| | - Lata Joshi
- Division of Molecular Genetics and Biochemistry, Molecular Biology Group, ICMR-National Institute of Cancer Prevention and Research, Noida, Uttar Pradesh, India
| | - Mausumi Bharadwaj
- Division of Molecular Genetics and Biochemistry, Molecular Biology Group, ICMR-National Institute of Cancer Prevention and Research, Noida, Uttar Pradesh, India.
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Xu R, Yiannikouris A, Shandilya UK, Karrow NA. Comparative Assessment of Different Yeast Cell Wall-Based Mycotoxin Adsorbents Using a Model- and Bioassay-Based In Vitro Approach. Toxins (Basel) 2023; 15:104. [PMID: 36728779 PMCID: PMC9959493 DOI: 10.3390/toxins15020104] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/18/2023] [Accepted: 01/20/2023] [Indexed: 01/27/2023] Open
Abstract
Frequently reported occurrences of deoxynivalenol (DON), beauvericin (BEA), and, to a lesser extent, ochratoxin A (OTA) and citrinin (CIT) in ruminant feed or feedstuff could represent a significant concern regarding feed safety, animal health, and productivity. Inclusion of yeast cell wall-based mycotoxin adsorbents in animal feeds has been a common strategy to mitigate adverse effects of mycotoxins. In the present study, an in vitro approach combining adsorption isotherm models and bioassays was designed to assess the efficacy of yeast cell wall (YCW), yeast cell wall extract (YCWE), and a postbiotic yeast cell wall-based blend (PYCW) products at the inclusion rate of 0.5% (w/v) (ratio of adsorbent mass to buffer solution volume). The Hill's adsorption isotherm model was found to best describe the adsorption processes of DON, BEA, and CIT. Calculated binding potential for YCW and YCWE using the Hill's model exhibited the same ranking for mycotoxin adsorption, indicating that BEA had the highest adsorption rate, followed by DON and CIT, which was the least adsorbed. PYCW had the highest binding potential for BEA compared with YCW and YCWE. In contrast, the Freundlich isotherm model presented a good fit for OTA adsorption by all adsorbents and CIT adsorption by PYCW. Results indicated that YCW was the most efficacious for sequestering OTA, whereas YCWE was the least efficacious. PYCW showed greater efficacy at adsorbing OTA than CIT. All adsorbents exhibited high adsorption efficacy for BEA, with an overall percentage average of bound mycotoxin exceeding 60%, whereas moderate efficacies for the other mycotoxins were observed (up to 37%). Differences in adsorbent efficacy of each adsorbent significantly varied according to experimental concentrations tested for each given mycotoxin (p < 0.05). The cell viability results from the bioassay using a bovine mammary epithelial cell line (MAC-T) indicated that all tested adsorbents could potentially mitigate mycotoxin-related damage to bovine mammary epithelium. Results from our studies suggested that all tested adsorbents had the capacity to adsorb selected mycotoxins in vitro, which could support their use to mitigate their effects in vivo.
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Affiliation(s)
- Ran Xu
- Department of Animal Biosciences, University of Guelph, Guelph, ON N1G2W1, Canada
| | - Alexandros Yiannikouris
- Alltech Inc., Center for Animal Nutrigenomics and Applied Animal Nutrition, 3031 Catnip Hill Road, Nicholasville, KY 40356, USA
| | - Umesh K. Shandilya
- Department of Animal Biosciences, University of Guelph, Guelph, ON N1G2W1, Canada
| | - Niel A. Karrow
- Department of Animal Biosciences, University of Guelph, Guelph, ON N1G2W1, Canada
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Xu R, Lou Y, Tidu A, Bulet P, Heinekamp T, Martin F, Brakhage A, Li Z, Liégeois S, Ferrandon D. The Toll pathway mediates Drosophila resilience to Aspergillus mycotoxins through specific Bomanins. EMBO Rep 2023; 24:e56036. [PMID: 36322050 PMCID: PMC9827548 DOI: 10.15252/embr.202256036] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/06/2022] [Accepted: 10/14/2022] [Indexed: 12/28/2022] Open
Abstract
Host defense against infections encompasses both resistance, which targets microorganisms for neutralization or elimination, and resilience/disease tolerance, which allows the host to withstand/tolerate pathogens and repair damages. In Drosophila, the Toll signaling pathway is thought to mediate resistance against fungal infections by regulating the secretion of antimicrobial peptides, potentially including Bomanins. We find that Aspergillus fumigatus kills Drosophila Toll pathway mutants without invasion because its dissemination is blocked by melanization, suggesting a role for Toll in host defense distinct from resistance. We report that mutants affecting the Toll pathway or the 55C Bomanin locus are susceptible to the injection of two Aspergillus mycotoxins, restrictocin and verruculogen. The vulnerability of 55C deletion mutants to these mycotoxins is rescued by the overexpression of Bomanins specific to each challenge. Mechanistically, flies in which BomS6 is expressed in the nervous system exhibit an enhanced recovery from the tremors induced by injected verruculogen and display improved survival. Thus, innate immunity also protects the host against the action of microbial toxins through secreted peptides and thereby increases its resilience to infection.
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Affiliation(s)
- Rui Xu
- Sino‐French Hoffmann InstituteGuangzhou Medical UniversityGuangzhouChina
- Université de StrasbourgStrasbourgFrance
- Modèles Insectes de l'Immunité InnéeUPR 9022 du CNRSStrasbourgFrance
| | - Yanyan Lou
- Sino‐French Hoffmann InstituteGuangzhou Medical UniversityGuangzhouChina
- Université de StrasbourgStrasbourgFrance
- Modèles Insectes de l'Immunité InnéeUPR 9022 du CNRSStrasbourgFrance
| | - Antonin Tidu
- Université de StrasbourgStrasbourgFrance
- Architecture et Réactivité de l'ARNUPR 9002 du CNRSStrasbourgFrance
| | - Philippe Bulet
- CR Université Grenoble Alpes, Institute for Advanced Biosciences, Inserm U1209CNRS UMR 5309GrenobleFrance
- Platform BioPark ArchampsArchampsFrance
| | - Thorsten Heinekamp
- Department of Molecular and Applied MicrobiologyLeibniz Institute for Natural Product Research and Infection Biology ‐ Hans Knöll Institute (Leibniz‐HKI)JenaGermany
| | - Franck Martin
- Université de StrasbourgStrasbourgFrance
- Architecture et Réactivité de l'ARNUPR 9002 du CNRSStrasbourgFrance
| | - Axel Brakhage
- Department of Molecular and Applied MicrobiologyLeibniz Institute for Natural Product Research and Infection Biology ‐ Hans Knöll Institute (Leibniz‐HKI)JenaGermany
- Institute of MicrobiologyFriedrich Schiller University JenaJenaGermany
| | - Zi Li
- Sino‐French Hoffmann InstituteGuangzhou Medical UniversityGuangzhouChina
| | - Samuel Liégeois
- Sino‐French Hoffmann InstituteGuangzhou Medical UniversityGuangzhouChina
- Université de StrasbourgStrasbourgFrance
- Modèles Insectes de l'Immunité InnéeUPR 9022 du CNRSStrasbourgFrance
| | - Dominique Ferrandon
- Sino‐French Hoffmann InstituteGuangzhou Medical UniversityGuangzhouChina
- Université de StrasbourgStrasbourgFrance
- Modèles Insectes de l'Immunité InnéeUPR 9022 du CNRSStrasbourgFrance
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Awais MM, Mehtab U, Anwar MI, Hameed MR, Akhtar M, Raza A, Aisha R, Muhammad F, Saleemi MK, Fayyaz A. Mitigation potential of individual and combined dietary supplementation of local Bentonite Clay and Distillery Sludge against Ochratoxin-A induced toxicity in broilers. BMC Vet Res 2022; 18:375. [PMID: 36261856 PMCID: PMC9580109 DOI: 10.1186/s12917-022-03466-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 09/27/2022] [Indexed: 11/12/2022] Open
Abstract
Background This study aimed to evaluate the ameliorative effects of dietary supplementation of local bentonite clay (BN) and distillery sludge (DS) alone and in combination on ochratoxin-A (OTA) induced toxicity in broilers. For this purpose, day-old-broiler chicks (n = 270) were procured from the local market and reared under standard management conditions. After 7 days of acclimatization, birds were divided into 2 main groups A and B with respect to OTA inclusion level in feed, each with four sub-groups viz. A1-A4, each challenged with OTA at a dietary inclusion level of 250 µg/kg feed and B1-B4, each challenged with OTA at the level of 500 µg/kg feed and a common control group that was fed with basal feed throughout the experiment. In groups A and B, BN and DS were administered with feed at the rate of 10 g/kg of feed and 5 g/kg of feed alone and in combination, respectively. Results Results showed that OTA administration alone resulted in poor feed conversion ratio (FCR) and immunological responses along with increased serum levels of alanine transaminase (ALT), Aspartate transaminase (AST), urea and creatinine (P < 0.05). A significant decrease (P < 0.05) in serum protein levels (albumin, globulin and total protein) was also observed in OTA-fed groups in a dose-dependent manner. The addition of BN at 10 g/kg of OTA-contaminated feed resulted in better FCR and immunological responses as compared to those fed OTA only. The BN supplementation also conferred protection against elevation of serum biochemical parameters when compared with OTA-fed groups. However, the addition of DS could not provide significant protection (P > 0.05) on alteration of serum biochemical parameters in response to the OTA induced toxicity. The combined supplementation of BN and DS resulted in amelioration of OTA-induced toxicity and showed improved FCR, immunological, hematological and serum biochemical parameters (P < 0.05) when compared with other groups. Similarly, BN and DS resulted in a significant decline (P < 0.05) in the OTA tissue residues compared with other groups and control. Conclusion In conclusion, combined dietary supplementation of BN (10 mg/kg) and DS (05 mg/kg) in feed reduced the toxic effects of OTA contamination at levels of 250 and 500 µg/kg of feed in broilers. So, the combination products of BN and DS may be successfully developed for use in poultry for protection against OTA-induced toxicity in broilers.
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Affiliation(s)
- Mian Muhammad Awais
- Department of Pathobiology, Faculty of Veterinary Sciences, Bahauddin Zakariya University, Multan, Pakistan.
| | - Ujala Mehtab
- Department of Pathobiology, Faculty of Veterinary Sciences, Bahauddin Zakariya University, Multan, Pakistan
| | - Muhammad Irfan Anwar
- Department of Pathobiology, Faculty of Veterinary Sciences, Bahauddin Zakariya University, Multan, Pakistan
| | - Muhammad Raza Hameed
- Department of Pathobiology, Faculty of Veterinary Sciences, Bahauddin Zakariya University, Multan, Pakistan
| | - Masood Akhtar
- Department of Pathobiology, Faculty of Veterinary Sciences, Bahauddin Zakariya University, Multan, Pakistan
| | - Ahmad Raza
- Department of Pathobiology, Faculty of Veterinary Sciences, Bahauddin Zakariya University, Multan, Pakistan
| | - Riffat Aisha
- Department of Biosciences, Faculty of Veterinary Sciences, Bahauddin Zakariya University, Multan, Pakistan
| | - Faqir Muhammad
- Department of Biosciences, Faculty of Veterinary Sciences, Bahauddin Zakariya University, Multan, Pakistan
| | | | - Ahad Fayyaz
- Department of Pathology, University of Agriculture, Faisalabad, Pakistan
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Talapko J, Meštrović T, Škrlec I. Growing importance of urogenital candidiasis in individuals with diabetes: A narrative review. World J Diabetes 2022; 13:809-821. [PMID: 36311997 PMCID: PMC9606786 DOI: 10.4239/wjd.v13.i10.809] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 08/06/2022] [Accepted: 09/07/2022] [Indexed: 02/05/2023] Open
Abstract
Both diabetes and fungal infections contribute significantly to the global disease burden, with increasing trends seen in most developed and developing countries during recent decades. This is reflected in urogenital infections caused by Candida species that are becoming ever more pervasive in diabetic patients, particularly those that present with unsatisfactory glycemic control. In addition, a relatively new group of anti-hyperglycemic drugs, known as sodium glucose cotransporter 2 inhibitors, has been linked with an increased risk for colonization of the urogenital region with Candida spp., which can subsequently lead to an infectious process. In this review paper, we have highlighted notable virulence factors of Candida species (with an emphasis on Candida albicans) and shown how the interplay of many pathophysiological factors can give rise to vulvovaginal candidiasis, potentially complicated with recurrences and dire pregnancy outcomes. We have also addressed an increased risk of candiduria and urinary tract infections caused by species of Candida in females and males with diabetes, further highlighting possible complications such as emphysematous cystitis as well as the risk for the development of balanitis and balanoposthitis in (primarily uncircumcised) males. With a steadily increasing global burden of diabetes, urogenital mycotic infections will undoubtedly become more prevalent in the future; hence, there is a need for an evidence-based approach from both clinical and public health perspectives.
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Affiliation(s)
- Jasminka Talapko
- Laboratory for Microbiology, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek 31000, Croatia
| | - Tomislav Meštrović
- University North, University Centre Varaždin, Varaždin 42000, Croatia
- Institute for Health Metrics and Evaluation, Department for Health Metrics Sciences, University of Washington School of Medicine, Seattle, Washington 98195, United States
| | - Ivana Škrlec
- Department of Biophysics, Biology, and Chemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek 31000, Croatia
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Ochratoxin A and Citrinin Differentially Modulate Bovine Mammary Epithelial Cell Permeability and Innate Immune Function. Toxins (Basel) 2022; 14:toxins14090640. [PMID: 36136578 PMCID: PMC9502480 DOI: 10.3390/toxins14090640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/08/2022] [Accepted: 09/12/2022] [Indexed: 11/29/2022] Open
Abstract
Frequent detection of mycotoxins ochratoxin A (OTA) and citrinin (CIT) in ruminant feed and feedstuff can be a potential threat to feed safety, animal performance and health. Ineffective biodegradation of these mycotoxins by rumen microflora following ingestion of contaminated feeds can lead to their circulatory transport to tissues such as mammary gland as the result of their biodistribution throughout the body. The bovine mammary epithelium plays a pivotal role in maintaining milk yield and composition and contributes to innate immune defense of the udder. The present study is the first to investigate individual effects of OTA and CIT on barrier and innate immune functions of the bovine mammary epithelium using a bovine mammary epithelial cell line (MAC-T). Results indicated that OTA and CIT exposure for 48 h significantly decreased cell viability in a concentration-dependent manner (p < 0.05). A decrease in transepithelial electrical resistance and increase in paracellular flux of FITC-40 kDa dextran was significantly induced by OTA treatment (p < 0.05), but not by CIT after 48 h exposure. qPCR was performed for assessment of expression of tight-junction proteins, Toll-like receptor 4 (TLR4) and cytokines after 4, 24 and 48 h of exposure. Both OTA and CIT markedly downregulated expression of claudin 3 and occludin (p < 0.05), whereas CIT did not affect zonula occludens-1 expression. Expression of TLR4 was significantly upregulated by OTA (p < 0.001) but downregulated by CIT (p < 0.05) at 48 h. Expression of IL-6, TNF-a and TGF-β was significantly upregulated by OTA (p < 0.05), whereas IL-6 and TGF-β expression was downregulated by CIT (p < 0.01). These results suggest that OTA and CIT could potentially differentially modulate barrier and innate immune functions of mammary epithelium. The present study not only throws light on the individual toxicity of each mycotoxin on bovine mammary epithelium but also lays the foundation for future studies on the combined effects of the two mycotoxins.
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31
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Donders G, Sziller IO, Paavonen J, Hay P, de Seta F, Bohbot JM, Kotarski J, Vives JA, Szabo B, Cepuliené R, Mendling W. Management of recurrent vulvovaginal candidosis: Narrative review of the literature and European expert panel opinion. Front Cell Infect Microbiol 2022; 12:934353. [PMID: 36159646 PMCID: PMC9504472 DOI: 10.3389/fcimb.2022.934353] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 08/08/2022] [Indexed: 11/19/2022] Open
Abstract
Recurrent vulvovaginal candidosis (RVVC) is a chronic, difficult to treat vaginal infection, caused by Candida species, which affects women of all ages and ethnic and social background. A long-term prophylactic maintenance regimen with antifungals is often necessary. In most clinical practice guidelines, oral fluconazole is recommended as the first-line treatment. Although clinical resistance to antifungal agents remains rare, overexposure to azoles may increase the development of fluconazole-resistant C. albicans strains. In addition, non-albicans Candida species are frequently dose-dependent susceptible or resistant to fluconazole and other azoles, and their prevalence is rising. Available therapeutic options to treat such fluconazole-resistant C. albicans and low susceptibility non-albicans strains are limited. Ten experts from different European countries discussed problematic issues of current RVVC diagnosis and treatment in two audiotaped online sessions and two electronic follow-up rounds. A total of 340 statements were transcribed, summarized, and compared with published evidence. The profile of patients with RVVC, their care pathways, current therapeutic needs, and potential value of novel drugs were addressed. Correct diagnosis, right treatment choice, and patient education to obtain adherence to therapy regimens are crucial for successful RVVC treatment. As therapeutic options are limited, innovative strategies are required. Well- tolerated and effective new drugs with an optimized mechanism of action are desirable and are discussed. Research into the impact of RVVC and treatments on health-related quality of life and sex life is also needed.
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Affiliation(s)
- Gilbert Donders
- Femicare VZW, Clinical Research for Women, Tienen, Belgium
- Department of Obstetrics and Gynecology, University Hospital Antwerp, Antwerp, Belgium
- Department of Obstetrics and Gynecology, Regional Hospital Tienen, Tienen, Belgium
| | - István Oszkár Sziller
- Dél-budai Centrumkórház, Szent Imre Egyetemi Oktatókórház, Szülészet és Nőgyógyászati Osztály, Budapest, Hungary
| | - Jorma Paavonen
- Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland
| | - Phillip Hay
- Guys and St. Thomas’ NHS Foundation Trust, London, United Kingdom
| | - Francesco de Seta
- Department of Medical, Surgical and Health Sciences, Institute for Maternal and Child Health, University of Trieste, IRCCS Burlo Garofolo, Trieste, Italy
| | - Jean Marc Bohbot
- Department of Sexually Transmitted Infections, Institut Alfred Fournier, Paris, France
| | - Jan Kotarski
- Department of Oncological Gynecology and Gynecology, Medical University of Lublin, Lublin, Poland
| | - Jordi Antoni Vives
- Department of Gynecology and Obstetrics, Hospital CIMA, Barcelona, Spain
| | - Bela Szabo
- Department of Obstetrics-Gynecology, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, Targu-Mures, Romania
| | | | - Werner Mendling
- Deutsches Zentrum für Infektionen in Gynäkologie und Geburtshilfe, Helios Universitätsklinikum Wuppertal, Wuppertal, Germany
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Solubility affects IL-1β-producing activity of the synthetic candidalysin peptide. PLoS One 2022; 17:e0273663. [PMID: 36040970 PMCID: PMC9426886 DOI: 10.1371/journal.pone.0273663] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 08/11/2022] [Indexed: 11/25/2022] Open
Abstract
Candidalysin, a peptide toxin produced specifically from hyphae of Candida albicans, plays a crucial role in C. albicans pathogenesis in the oral cavity and vagina. Synthetic peptides have been widely used in previous studies to investigate the bioactivity of candidalysin. Although the solubility of the peptide, which is expected to have a hydrophobic property, has not been well characterized, candidalysin solutions are usually prepared in water. In this study, we prepared the synthetic peptide candidalysin in water (CLw) or in dimethyl sulfoxide (CLd) and compared their cytotoxicity and interleukin (IL)-1β-producing activity to determine whether the activity of the peptide would be affected. In addition, we evaluated whether the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway or other pathways were involved in their activities. Unexpectedly, we found that CLw was not completely solubilized and contained abundant insoluble microparticles. CLw was active at comparably high concentrations (≥ 10 μM). In contrast, CLd is completely solubilized and sufficiently active at low concentrations, that is, 1 μM or less. CLw showed weak cytotoxicity and NLRP3-dependent and cathepsin B-dependent IL-1β-producing activity, whereas CLd showed strong cytotoxicity and cathepsin B-dependent IL-1β-producing activity. Fractionation of CLw revealed that NLRP3-dependent activity was caused by insoluble microparticles. Furthermore, nanoparticle tracking of CLd revealed that the peptide was present as nanoparticles with a size of 96 nm. CLw contained a small amount of such nanoparticles. Thus, the bioactivities of the synthetic peptide candidalysin, especially the IL-1β-producing activity, are affected by the solubility of the peptide depending on the solvent employed. The NLRP3-dependent activity of the synthetic peptide is caused by insoluble microparticles and may not be the intrinsic activity of candidalysin.
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33
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Functional and Immunological Studies Revealed a Second Superantigen Toxin in Staphylococcal Enterotoxin C Producing Staphylococcus aureus Strains. Toxins (Basel) 2022; 14:toxins14090595. [PMID: 36136533 PMCID: PMC9504012 DOI: 10.3390/toxins14090595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/21/2022] [Accepted: 07/26/2022] [Indexed: 11/16/2022] Open
Abstract
Staphylococcus aureus is a human and animal pathogen as well as a commensal bacterium. It can be a causative agent of severe, life-threatening infections with high mortality, e.g., toxic shock syndrome, septic shock, and multi-organ failure. S. aureus strains secrete a number of toxins. Exotoxins/enterotoxins are considered important in the pathogenesis of the above-mentioned conditions. Exotoxins, e.g., superantigen toxins, cause uncontrolled and polyclonal T cell activation and unregulated activation of inflammatory cytokines. Here we show the importance of genomic analysis of infectious strains in order to identify disease-causing exotoxins. Further, we show through functional analysis of superantigenic properties of staphylococcal exotoxins that even very small amounts of a putative superantigenic contaminant can have a significant mitogenic effect. The results show expression and production of two distinct staphylococcal exotoxins, SEC and SEL, in several strains from clinical isolates. Antibodies against both toxins are required to neutralise the superantigenic activity of staphylococcal supernatants and purified staphylococcal toxins.
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34
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Chancharoenthana W, Sutnu N, Visitchanakun P, Sawaswong V, Chitcharoen S, Payungporn S, Schuetz A, Schultz MJ, Leelahavanichkul A. Critical roles of sepsis-reshaped fecal virota in attenuating sepsis severity. Front Immunol 2022; 13:940935. [PMID: 35983067 PMCID: PMC9380439 DOI: 10.3389/fimmu.2022.940935] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 07/11/2022] [Indexed: 11/13/2022] Open
Abstract
Because studies on all fecal organisms (bacteria, fungi, and viruses) in sepsis are rare and bacteriophages during sepsis might have adapted against gut bacteria with possible pathogenicity, cecal ligation and puncture (CLP; a sepsis mouse model) was evaluated. In fecal bacteriome, sepsis increased Bacteroides and Proteobacteria but decreased Firmicutes, while fecal virome demonstrated increased Podoviridae when compared with sham feces. There was no difference in the fungal microbiome (predominant Ascomycota in both sham and CLP mice) and the abundance of all organisms between sepsis and control groups. Interestingly, the transfers of feces from CLP mice worsened sepsis severity when compared with sham fecal transplantation, as evaluated by mortality, renal injury (serum creatinine and histology), liver damage (liver enzyme and histology), spleen apoptosis, serum cytokines, endotoxemia, and bacteremia. In contrast, the transfers of fecal viral particles from sepsis mice, but not from sham mice, attenuated inflammation in CLP sepsis possibly through the decrease in several fecal pathogenic bacteria (such as Proteobacteria, Gammaproteobacteria, and Prevotellaceae) as evaluated by fecal microbiome analysis. Perhaps the isolation of favorable bacteriophages in sepsis feces and increased abundance ex vivo before oral treatment in a high concentration are beneficial.
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Affiliation(s)
- Wiwat Chancharoenthana
- Tropical Nephrology Research Unit, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Tropical Immunology and Translational Research Unit, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- *Correspondence: Wiwat Chancharoenthana, ; Asada Leelahavanichkul,
| | - Nattawut Sutnu
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence on Translational Research in Inflammatory and Immunology (CETRII), Department of Microbiology, Chulalongkorn University, Bangkok, Thailand
| | - Peerapat Visitchanakun
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence on Translational Research in Inflammatory and Immunology (CETRII), Department of Microbiology, Chulalongkorn University, Bangkok, Thailand
| | - Vorthon Sawaswong
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Research Unit of Systems Microbiology, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Suwalak Chitcharoen
- Research Unit of Systems Microbiology, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sunchai Payungporn
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Research Unit of Systems Microbiology, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Alexandra Schuetz
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda , MD, United States
- Department of Retrovirology, Armed Forces Research Institute of Medical Sciences-United States Component, Bangkok, Thailand
| | - Marcus J. Schultz
- Mahidol–Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Department of Intensive Care & Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A), Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom
| | - Asada Leelahavanichkul
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence on Translational Research in Inflammatory and Immunology (CETRII), Department of Microbiology, Chulalongkorn University, Bangkok, Thailand
- *Correspondence: Wiwat Chancharoenthana, ; Asada Leelahavanichkul,
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Yaakoub H, Mina S, Calenda A, Bouchara JP, Papon N. Oxidative stress response pathways in fungi. Cell Mol Life Sci 2022; 79:333. [PMID: 35648225 PMCID: PMC11071803 DOI: 10.1007/s00018-022-04353-8] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 04/21/2022] [Accepted: 05/05/2022] [Indexed: 11/03/2022]
Abstract
Fungal response to any stress is intricate, specific, and multilayered, though it employs only a few evolutionarily conserved regulators. This comes with the assumption that one regulator operates more than one stress-specific response. Although the assumption holds true, the current understanding of molecular mechanisms that drive response specificity and adequacy remains rudimentary. Deciphering the response of fungi to oxidative stress may help fill those knowledge gaps since it is one of the most encountered stress types in any kind of fungal niche. Data have been accumulating on the roles of the HOG pathway and Yap1- and Skn7-related pathways in mounting distinct and robust responses in fungi upon exposure to oxidative stress. Herein, we review recent and most relevant studies reporting the contribution of each of these pathways in response to oxidative stress in pathogenic and opportunistic fungi after giving a paralleled overview in two divergent models, the budding and fission yeasts. With the concept of stress-specific response and the importance of reactive oxygen species in fungal development, we first present a preface on the expanding domain of redox biology and oxidative stress.
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Affiliation(s)
- Hajar Yaakoub
- Univ Angers, Univ Brest, IRF, SFR ICAT, 49000, Angers, France
| | - Sara Mina
- Department of Medical Laboratory Sciences, Faculty of Health Sciences, Beirut Arab University, Beirut, Lebanon
| | | | | | - Nicolas Papon
- Univ Angers, Univ Brest, IRF, SFR ICAT, 49000, Angers, France.
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Viegas C, Cervantes R, Dias M, Gomes B, Pena P, Carolino E, Twarużek M, Kosicki R, Soszczyńska E, Viegas S, Caetano LA. Six Feet under Microbiota: Microbiologic Contamination and Toxicity Profile in Three Urban Cemeteries from Lisbon, Portugal. Toxins (Basel) 2022; 14:toxins14050348. [PMID: 35622594 PMCID: PMC9146229 DOI: 10.3390/toxins14050348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 05/10/2022] [Accepted: 05/13/2022] [Indexed: 11/23/2022] Open
Abstract
Cemeteries are potential environmental reservoirs of pathogenic microorganisms from organic matter decomposition. This study aimed to characterize the microbial contamination in three cemeteries, and more specifically in grave diggers’ facilities. One active sampling method (impingement method) and several passive sampling methods (swabs, settled dust, settled dust filters and electrostatic dust cloths—EDC) were employed. The molecular detection of Aspergillus sections and SARS-CoV-2, as well as mycotoxin analysis, screening of azole resistance, and cytotoxicity measurement were also conducted. Total bacteria contamination was 80 CFU·m−2 in settled dust samples, reached 849 CFU·m−2 in EDC and 20,000 CFU·m−2 in swabs, and ranged from 5000 to 10,000 CFU·m−2 in filters. Gram-negative bacteria (VRBA) were only observed in in settled dust samples (2.00 × 105 CFU·m−2). Regarding Aspergillus sp., the highest counts were obtained in DG18 (18.38%) and it was not observed in azole-supplemented SDA media. SARS-CoV-2 and the targeted Aspergillus sections were not detected. Mycophenolic acid was detected in one settled dust sample. Cytotoxic effects were observed for 94.4% filters and 5.6% EDC in A549 lung epithelial cells, and for 50.0% filters and 5.6% EDC in HepG2 cells. Future studies are needed in this occupational setting to implement more focused risk management measures.
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Affiliation(s)
- Carla Viegas
- H&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia e Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal; (R.C.); (M.D.); (B.G.); (P.P.); (E.C.); (S.V.); (L.A.C.)
- NOVA National School of Public Health, Public Health Research Centre, Universidade Nova de Lisboa, 1099-085 Lisbon, Portugal
- Comprehensive Health Research Center (CHRC), NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
- Correspondence:
| | - Renata Cervantes
- H&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia e Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal; (R.C.); (M.D.); (B.G.); (P.P.); (E.C.); (S.V.); (L.A.C.)
| | - Marta Dias
- H&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia e Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal; (R.C.); (M.D.); (B.G.); (P.P.); (E.C.); (S.V.); (L.A.C.)
- NOVA National School of Public Health, Public Health Research Centre, Universidade Nova de Lisboa, 1099-085 Lisbon, Portugal
- Comprehensive Health Research Center (CHRC), NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
| | - Bianca Gomes
- H&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia e Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal; (R.C.); (M.D.); (B.G.); (P.P.); (E.C.); (S.V.); (L.A.C.)
| | - Pedro Pena
- H&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia e Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal; (R.C.); (M.D.); (B.G.); (P.P.); (E.C.); (S.V.); (L.A.C.)
| | - Elisabete Carolino
- H&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia e Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal; (R.C.); (M.D.); (B.G.); (P.P.); (E.C.); (S.V.); (L.A.C.)
| | - Magdalena Twarużek
- Department of Physiology and Toxicology, Institute of Experimental Biology, Faculty of Natural Sciences, Kazimierz Wielki University, Chodkiewicza 30, 85–064 Bydgoszcz, Poland; (M.T.); (R.K.); (E.S.)
| | - Robert Kosicki
- Department of Physiology and Toxicology, Institute of Experimental Biology, Faculty of Natural Sciences, Kazimierz Wielki University, Chodkiewicza 30, 85–064 Bydgoszcz, Poland; (M.T.); (R.K.); (E.S.)
| | - Ewelina Soszczyńska
- Department of Physiology and Toxicology, Institute of Experimental Biology, Faculty of Natural Sciences, Kazimierz Wielki University, Chodkiewicza 30, 85–064 Bydgoszcz, Poland; (M.T.); (R.K.); (E.S.)
| | - Susana Viegas
- H&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia e Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal; (R.C.); (M.D.); (B.G.); (P.P.); (E.C.); (S.V.); (L.A.C.)
- NOVA National School of Public Health, Public Health Research Centre, Universidade Nova de Lisboa, 1099-085 Lisbon, Portugal
- Comprehensive Health Research Center (CHRC), NOVA Medical School, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
| | - Liliana Aranha Caetano
- H&TRC—Health & Technology Research Center, ESTeSL—Escola Superior de Tecnologia e Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal; (R.C.); (M.D.); (B.G.); (P.P.); (E.C.); (S.V.); (L.A.C.)
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, 1649-003 Lisbon, Portugal
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Bartholomew HP, Bradshaw MJ, Macarisin O, Gaskins VL, Fonseca JM, Jurick WM. More than a Virulence Factor: Patulin Is a Non-Host-Specific Toxin that Inhibits Postharvest Phytopathogens and Requires Efflux for Penicillium Tolerance. PHYTOPATHOLOGY 2022; 112:1165-1174. [PMID: 35365059 DOI: 10.1094/phyto-09-21-0371-r] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Mycotoxin contamination is a leading cause of food spoilage and waste on a global scale. Patulin, a mycotoxin produced by Penicillium spp. during postharvest pome fruit decay, causes acute and chronic effects in humans, withstands pasteurization, and is not eliminated by fermentation. While much is known about the impact of patulin on human health, there are significant knowledge gaps concerning the effect of patulin during postharvest fruit-pathogen interactions. Application of patulin on six apple cultivars reproduced some blue mold symptoms that were cultivar-independent and dose-dependent. Identical symptoms were also observed in pear and mandarin orange. Six Penicillium isolates exposed to exogenous patulin exhibited delayed germination after 24 h, yet all produced viable colonies in 7 days. However, four common postharvest phytopathogenic fungi were completely inhibited by patulin during conidial germination and growth, suggesting the toxin is important for Penicillium to dominate the postharvest niche. Using clorgyline, a broad-spectrum efflux pump inhibitor, we demonstrated that efflux plays a role in Penicillium auto-resistance to patulin during conidial germination. The work presented here contributes new knowledge of patulin auto-resistance, its mode of action, and inhibitory role in fungal-fungal interactions. Our findings provide a solid foundation to develop toxin and decay mitigation approaches.
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Affiliation(s)
- Holly P Bartholomew
- Food Quality Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705
| | - Michael J Bradshaw
- Food Quality Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705
| | - Otilia Macarisin
- Food Quality Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705
| | - Verneta L Gaskins
- Food Quality Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705
| | - Jorge M Fonseca
- Food Quality Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705
| | - Wayne M Jurick
- Food Quality Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705
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Mycotoxin Interactions along the Gastrointestinal Tract: In Vitro Semi-Dynamic Digestion and Static Colonic Fermentation of a Contaminated Meal. Toxins (Basel) 2022; 14:toxins14010028. [PMID: 35051005 PMCID: PMC8779761 DOI: 10.3390/toxins14010028] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 12/16/2021] [Accepted: 12/23/2021] [Indexed: 02/04/2023] Open
Abstract
Aflatoxin B1 (AFB1) and ochratoxin A (OTA) naturally co-occur in several foods, but no studies have followed the fate of mycotoxins' interactions along the gastrointestinal tract using in vitro digestion models. This study used a novel semi-dynamic model that mimics gradual acidification and gastric emptying, coupled with a static colonic fermentation phase, in order to monitor mycotoxins' bioaccessibility by the oral route. AFB1 and OTA bioaccessibility patterns differed in single or co-exposed scenarios. When co-exposed (MIX meal), AFB1 bioaccessibility at the intestinal level increased by ~16%, while OTA bioaccessibility decreased by ~20%. Additionally, a significant increase was observed in both intestinal cell viability and NO production. With regard to mycotoxin-probiotic interactions, the MIX meal showed a null effect on Lactobacillus and Bifidobacterium strain growth, while isolated AFB1 reduced bacterial growth parameters. These results were confirmed at phylum and family levels using a gut microbiota approach. After colonic fermentation, the fecal supernatant did not trigger the NF-kB activation pathway, indicating reduced toxicity of mycotoxins. In conclusion, if single exposed, AFB1 will have a significant impact on intestinal viability and probiotic growth, while OTA will mostly trigger NO production; in a co-exposure situation, both intestinal viability and inflammation will be affected, but the impact on probiotic growth will be neglected.
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Herbal Immunity Booster-Associated Liver Injury During COVID-19 Pandemic and Aflatoxins. J Clin Exp Hepatol 2022; 12:252-253. [PMID: 34462625 PMCID: PMC8388140 DOI: 10.1016/j.jceh.2021.08.021] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 08/22/2021] [Indexed: 12/12/2022] Open
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Mold, Mycotoxins and a Dysregulated Immune System: A Combination of Concern? Int J Mol Sci 2021; 22:ijms222212269. [PMID: 34830149 PMCID: PMC8619365 DOI: 10.3390/ijms222212269] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/09/2021] [Accepted: 11/10/2021] [Indexed: 12/14/2022] Open
Abstract
Fungi represent one of the most diverse and abundant eukaryotes on earth. The interplay between mold exposure and the host immune system is still not fully elucidated. Literature research focusing on up-to-date publications is providing a heterogenous picture of evidence and opinions regarding the role of mold and mycotoxins in the development of immune diseases. While the induction of allergic immune responses by molds is generally acknowledged, other direct health effects like the toxic mold syndrome are controversially discussed. However, recent observations indicate a particular importance of mold/mycotoxin exposure in individuals with pre-existing dysregulation of the immune system, due to exacerbation of underlying pathophysiology including allergic and non-allergic chronic inflammatory diseases, autoimmune disorders, and even human immunodeficiency virus (HIV) disease progression. In this review, we focus on the impact of mycotoxins regarding their impact on disease progression in pre-existing immune dysregulation. This is complemented by experimental in vivo and in vitro findings to present cellular and molecular modes of action. Furthermore, we discuss hypothetical mechanisms of action, where evidence is missing since much remains to be discovered.
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Cytotoxicity of Aspergillus Section Fumigati Isolated from Health Care Environments. J Fungi (Basel) 2021; 7:jof7100839. [PMID: 34682260 PMCID: PMC8539694 DOI: 10.3390/jof7100839] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 10/05/2021] [Accepted: 10/05/2021] [Indexed: 01/04/2023] Open
Abstract
This study analyzed 57 Aspergillus section Fumigati (AF) isolates collected by active and passive sampling (N = 450) in several health care facilities and from biological sampling of health care workers (N = 25) and controls (N = 22) in Portugal. All isolates were cultured in different media and screened for azole resistance. Cytotoxicity was assessed for 40 isolates in lung epithelial cells and kidney cells using the MTT assay. Aspergillus section Fumigati was prevalent in the health care facilities and in nasal swabs from health care workers and controls. All AF isolates reduced cell viability and presented medium to high cytotoxicity, with cytotoxicity being significantly higher in A549 lung epithelial cells. The cytotoxicity of isolates from air and nasal swab samples suggested the inhalation route as a risk factor. Notably, 42% of AF isolates exhibited a pattern of reduced susceptibility to some of the most used antifungals available for the treatment of patients infected with these fungi. In sum, the epidemiology and clinical relevance of Aspergillus section Fumigati should continue to be addressed. A deeper understanding of the mechanisms underlying Aspergillus-mediated cytotoxicity is necessary.
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Aflatoxin Biosynthesis, Genetic Regulation, Toxicity, and Control Strategies: A Review. J Fungi (Basel) 2021; 7:jof7080606. [PMID: 34436145 PMCID: PMC8397101 DOI: 10.3390/jof7080606] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 07/19/2021] [Accepted: 07/22/2021] [Indexed: 12/24/2022] Open
Abstract
Aflatoxins (AFs) are highly toxic and cancer-causing compounds, predominantly synthesized by the Aspergillus species. AFs biosynthesis is a lengthy process that requires as minimum as 30 genes grouped inside 75 kilobytes (kB) of gene clusters, which are regulated by specific transcription factors, including aflR, aflS, and some general transcription factors. This paper summarizes the status of research on characterizing structural and regulatory genes associated with AF production and their roles in aflatoxigenic fungi, particularly Aspergillus flavus and A. parasiticus, and enhances the current understanding of AFs that adversely affect humans and animals with a great emphasis on toxicity and preventive methods.
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