|
1
|
Shi Z, Li Y, Shi W, Mu Z, Han Q, Zhang W. Glutamicibacter sp. ZY1 antagonizes pathogenic Vibrio parahaemolyticus via iron competition. Appl Environ Microbiol 2025; 91:e0000925. [PMID: 40272177 DOI: 10.1128/aem.00009-25] [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: 01/02/2025] [Accepted: 02/19/2025] [Indexed: 04/25/2025] Open
Abstract
Probiotics are prior agents for treating bacterial infection with advantages of inhibiting pathogenic bacteria and improving immune responses of hosts, thus increasing the survival rate of cultured animals. In this study, one Vibrio parahaemolyticus YDE17 pathogenic to shrimp and its antagonist Glutamicibacter sp. ZY1 were screened, and ZY1 showed stable inhibitory effects on diverse Vibrio spp., especially V. parahaemolyticus. ZY1 secreted inhibitory substances into supernatant, and the activity of inhibitory substances did not change after being treated under different temperatures, proteinase K, and pH (6-10), which indicated that the inhibitory substances might be small molecules, which led us to trace the siderophore production. The siderophore production of YDE17 co-incubated with the cell-free supernatant of ZY1 was greater than that of YDE17 alone, which indicated that the cell-free supernatant of ZY1 created iron-limiting conditions for YDE17. This finding was confirmed by iron supplementation assays, in which the inhibitory activity of the cell-free supernatant of ZY1 on YDE17 as well as the siderophore production of YDE17 decreased in the presence of FeCl3. The effect of iron on inhibition was further confirmed by in vivo infection. The relative percent survival of ZY1 to shrimp challenged by YDE17 was 83.3%, but the survival rates of shrimp challenged with YDE17/ZY1/FeCl3 were similar to that of YDE17, both of which were significantly lower than the 70% survival rate of shrimps simultaneously challenged by ZY1/YDE17. Our study offers a new probiotic resource to control vibriosis, which works through iron competition with the opportunistic pathogens of Vibrio spp.IMPORTANCEBacteria belonging to Vibrio spp., especially Vibrio parahaemolyticus, are important opportunistic pathogens infecting a wide range of hosts including fish, shrimp, shellfish, and crab. Antibiotics are effective but show the disadvantages of antibiotic generation, microecology destruction, and biological toxicology; thus, new treatments of Vibrio infection are urgently recommended. In our present study, Glutamicibacter sp. ZY1, belonging to the phylum Actinomycetes, was selected and showed high inhibitory activity to inhibit V. parahaemolyticus pathogenic to shrimp. Glutamicibacter sp. ZY1 antagonized V. parahaemolyticus YDE17 through producing siderophore to compete for iron, based on the results of both in vitro and in vivo experiments under different iron levels. This study offers a new strategy to control Vibrio infection in aquaculture.
Collapse
Affiliation(s)
- Zhili Shi
- School of Marine Sciences, Ningbo University, Ningbo, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo, China
| | - Ya Li
- School of Marine Sciences, Ningbo University, Ningbo, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo, China
| | - Weibo Shi
- School of Marine Sciences, Ningbo University, Ningbo, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo, China
| | - Zhixin Mu
- School of Marine Sciences, Ningbo University, Ningbo, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo, China
| | - Qingxi Han
- School of Marine Sciences, Ningbo University, Ningbo, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo, China
| | - Weiwei Zhang
- School of Marine Sciences, Ningbo University, Ningbo, China
- Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo, China
| |
Collapse
|
|
2
|
Niu L, Wang H, Luo G, Zhou J, Hu Z, Yan B. Advances in understanding immune homeostasis in latent tuberculosis infection. WIREs Mech Dis 2024; 16:e1643. [PMID: 38351551 DOI: 10.1002/wsbm.1643] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 01/19/2024] [Accepted: 01/19/2024] [Indexed: 07/13/2024]
Abstract
Nearly one-fourth of the global population is infected by Mycobacterium tuberculosis (Mtb), and approximately 90%-95% remain asymptomatic as latent tuberculosis infection (LTBI), an estimated 5%-10% of those with latent infections will eventually progress to active tuberculosis (ATB). Although it is widely accepted that LTBI transitioning to ATB results from a disruption of host immune balance and a weakening of protective immune responses, the exact underlying immunological mechanisms that promote this conversion are not well characterized. Thus, it is difficult to accurately predict tuberculosis (TB) progression in advance, leaving the LTBI population as a significant threat to TB prevention and control. This article systematically explores three aspects related to the immunoregulatory mechanisms and translational research about LTBI: (1) the distinct immunocytological characteristics of LTBI and ATB, (2) LTBI diagnostic markers discovery related to host anti-TB immunity and metabolic pathways, and (3) vaccine development focus on LTBI. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology Infectious Diseases > Genetics/Genomics/Epigenetics Immune System Diseases > Genetics/Genomics/Epigenetics.
Collapse
Affiliation(s)
- Liangfei Niu
- Center for Tuberculosis Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People's Republic of China
| | - Hao Wang
- Center for Tuberculosis Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People's Republic of China
- School of Life Science and Technology, Wuhan Polytechnic University, Wuhan, China
| | - Geyang Luo
- Center for Tuberculosis Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People's Republic of China
| | - Jing Zhou
- Department of Pathology, Center for Tuberculosis Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People's Republic of China
| | - Zhidong Hu
- Center for Tuberculosis Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People's Republic of China
| | - Bo Yan
- Center for Tuberculosis Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People's Republic of China
| |
Collapse
|
|
3
|
Gao Y, Liu S, Huang Y, Li F, Zhang Y. Regulation of anti-tumor immunity by metal ion in the tumor microenvironment. Front Immunol 2024; 15:1379365. [PMID: 38915413 PMCID: PMC11194341 DOI: 10.3389/fimmu.2024.1379365] [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: 01/31/2024] [Accepted: 05/29/2024] [Indexed: 06/26/2024] Open
Abstract
Metal ions play an essential role in regulating the functions of immune cells by transmitting intracellular and extracellular signals in tumor microenvironment (TME). Among these immune cells, we focused on the impact of metal ions on T cells because they can recognize and kill cancer cells and play an important role in immune-based cancer treatment. Metal ions are often used in nanomedicines for tumor immunotherapy. In this review, we discuss seven metal ions related to anti-tumor immunity, elucidate their roles in immunotherapy, and provide novel insights into tumor immunotherapy and clinical applications.
Collapse
Affiliation(s)
- Yaoxin Gao
- Biotherapy Center & Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shasha Liu
- Biotherapy Center & Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yifan Huang
- Biotherapy Center & Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Feng Li
- Biotherapy Center & Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yi Zhang
- Biotherapy Center & Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- School of Life Sciences, Zhengzhou University, Zhengzhou, China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
- School of Public Health, Zhengzhou University, Zhengzhou, China
| |
Collapse
|
|
4
|
Hurrell BP, Sakano Y, Shen S, Helou DG, Li M, Shafiei-Jahani P, Kazemi MH, Sakano K, Li X, Quach C, Barbers R, Akbari O. Iron controls the development of airway hyperreactivity by regulating ILC2 metabolism and effector function. Sci Transl Med 2024; 16:eadk4728. [PMID: 38718131 DOI: 10.1126/scitranslmed.adk4728] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 04/09/2024] [Indexed: 11/06/2024]
Abstract
Group 2 innate lymphoid cells (ILC2s) rapidly induce a type 2 inflammation in the lungs in response to allergens. Here, we focused on the role of iron, a critical nutritional trace element, on ILC2 function and asthma pathogenesis. We found that transferrin receptor 1 (TfR1) is rapidly up-regulated and functional during ILC2 activation in the lungs, and blocking transferrin uptake reduces ILC2 expansion and activation. Iron deprivation reprogrammed ILC2 metabolism, inducing a HIF-1α-driven up-regulation of glycolysis and inhibition of oxidative mitochondrial activity. Consequently, we observed that in vivo iron chelation or induction of hypoferremia reduced the development of airway hyperreactivity in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s rapidly induced TfR1 during activation, whereas inhibition of iron uptake or iron deprivation reduced effector functions. Last, we found a negative relationship between circulating ILC2 TfR1 expression and airway function in cohorts of patients with asthma. Collectively, our studies define cellular iron as a critical regulator of ILC2 function.
Collapse
Affiliation(s)
- Benjamin P Hurrell
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Yoshihiro Sakano
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Stephen Shen
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Doumet Georges Helou
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Meng Li
- USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, CA 90033, USA
| | - Pedram Shafiei-Jahani
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Mohammad Hossein Kazemi
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Kei Sakano
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Xin Li
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Christine Quach
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Richard Barbers
- Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Omid Akbari
- Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| |
Collapse
|
|
5
|
Leon J, Sarkar S, Basu D, Nanda N, Joseph NM. Anaemia of chronic disease among pulmonary tuberculosis patients is associated with inflammatory marker at the start of intensive phase. J Family Med Prim Care 2024; 13:1316-1327. [PMID: 38827693 PMCID: PMC11141999 DOI: 10.4103/jfmpc.jfmpc_1374_23] [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: 08/21/2023] [Revised: 10/19/2023] [Accepted: 11/17/2023] [Indexed: 06/04/2024] Open
Abstract
Background Tuberculosis (TB) disrupts iron balance through systemic inflammation. Pulmonary tuberculosis (PTB) is linked to diverse anaemia types, necessitating intricate haematological and biochemical assessments for diagnosis. This study aims to describe the prevalence of anaemia of chronic disease (ACD), iron deficiency anaemia (IDA) among PTB patients and factors associated with these types of anaemia. Methods A cross-sectional analysis was conducted from community-based cohort study involving sputum-positive PTB patients from 2018 to 2020 in urban Puducherry. Participants were enrolled from 10 primary health centres within 2 weeks of initiating anti-tubercular treatment (ATT). Blood samples were collected for assessing haematological and biochemical parameters. The sTfR/log ferritin ratio was used to distinguish between ACD and IDA. Data were captured using Epicollect5 and analysed using STATA V14. Result Of the 176 PTB patients included, 63.07% (111/176) had anaemia, with ACD being the predominant type (84.6%, 94/111). The C-reactive protein (CRP) levels were higher among the anaemic group [40.77 (16.66-58.51) mg/dl vs 24.65 (14.23-47.26) mg/dl] and higher among the ACD as compared to IDA [46.9 (22.3-61.2) vs 20.8 (13.0-39.1) mg/dl]. Undernourished [adjusted prevalence ratio (APR) =3.43; confidence interval (CI): 1.21-9.69] and patients having low risk of dependence on tobacco [APR = 1.52; CI: 1.10-2.11] had higher risk of ACD. Female patients had higher risk of IDA [APR = 4.95, P < 0.01]. Conclusion The largest proportion of the PTB participants with anaemia had ACD. Acute-phase reactant and inflammatory marker are increased among newly diagnosed new sputum smear-positive (NSP) PTB participants at the start of ATT. Addressing inflammation is needed for combating anaemia in PTB patients.
Collapse
Affiliation(s)
- Jovita Leon
- Department of Preventive and Social Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Sonali Sarkar
- Department of Preventive and Social Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Debdatta Basu
- Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Nivedita Nanda
- Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Noyal Mariya Joseph
- Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| |
Collapse
|
|
6
|
Ying Z, Yin M, Zhu Z, Shang Z, Pei Y, Liu J, Liu Q. Iron Stress Affects the Growth and Differentiation of Toxoplasma gondii. Int J Mol Sci 2024; 25:2493. [PMID: 38473741 PMCID: PMC10931281 DOI: 10.3390/ijms25052493] [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: 01/06/2024] [Revised: 02/07/2024] [Accepted: 02/14/2024] [Indexed: 03/14/2024] Open
Abstract
Iron is an indispensable nutrient for the survival of Toxoplasma gondii; however, excessive amounts can lead to toxicity. The parasite must overcome the host's "nutritional immunity" barrier and compete with the host for iron. Since T. gondii can infect most nucleated cells, it encounters increased iron stress during parasitism. This study assessed the impact of iron stress, encompassing both iron depletion and iron accumulation, on the growth of T. gondii. Iron accumulation disrupted the redox balance of T. gondii while enhancing the parasite's ability to adhere in high-iron environments. Conversely, iron depletion promoted the differentiation of tachyzoites into bradyzoites. Proteomic analysis further revealed proteins affected by iron depletion and identified the involvement of phosphotyrosyl phosphatase activator proteins in bradyzoite formation.
Collapse
Affiliation(s)
- Zhu Ying
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China; (Z.Y.); (M.Y.); (Z.Z.); (Z.S.); (Y.P.); (J.L.)
- Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
- National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
| | - Meng Yin
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China; (Z.Y.); (M.Y.); (Z.Z.); (Z.S.); (Y.P.); (J.L.)
- Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
- National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
| | - Zifu Zhu
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China; (Z.Y.); (M.Y.); (Z.Z.); (Z.S.); (Y.P.); (J.L.)
- Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
- National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
| | - Zheng Shang
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China; (Z.Y.); (M.Y.); (Z.Z.); (Z.S.); (Y.P.); (J.L.)
- Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
- National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
| | - Yanqun Pei
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China; (Z.Y.); (M.Y.); (Z.Z.); (Z.S.); (Y.P.); (J.L.)
- Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
- National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
| | - Jing Liu
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China; (Z.Y.); (M.Y.); (Z.Z.); (Z.S.); (Y.P.); (J.L.)
- Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
- National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
| | - Qun Liu
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China; (Z.Y.); (M.Y.); (Z.Z.); (Z.S.); (Y.P.); (J.L.)
- Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
- National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China
| |
Collapse
|
|
7
|
Fang ZX, Chen WJ, Wu Z, Hou YY, Lan YZ, Wu HT, Liu J. Inflammatory response in gastrointestinal cancers: Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications. World J Clin Oncol 2024; 15:9-22. [PMID: 38292664 PMCID: PMC10823946 DOI: 10.5306/wjco.v15.i1.9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 11/24/2023] [Accepted: 12/19/2023] [Indexed: 01/23/2024] Open
Abstract
Chronic inflammation is known to increase the risk of gastrointestinal cancers (GICs), the common solid tumors worldwide. Precancerous lesions, such as chronic atrophic inflammation and ulcers, are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis. Unfortunately, due to the lack of effective therapeutic targets, the prognosis of patients with GICs is still unsatisfactory. Interestingly, it is found that six transmembrane epithelial antigens of the prostate (STEAPs), a group of metal reductases, are significantly associated with the progression of malignancies, playing a crucial role in systemic metabolic homeostasis and inflammatory responses. The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress, responding to inflammatory reactions. Under the imbalance status of abnormal oxidative stress, STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process. This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms, with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.
Collapse
Affiliation(s)
- Ze-Xuan Fang
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Wen-Jia Chen
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Zheng Wu
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yan-Yu Hou
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yang-Zheng Lan
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Hua-Tao Wu
- Department of General Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Jing Liu
- The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| |
Collapse
|
|
8
|
de Miranda R, Cuthbert BJ, Klevorn T, Chao A, Mendoza J, Arbing M, Sieminski PJ, Papavinasasundaram K, Abdul-Hafiz S, Chan S, Sassetti CM, Ehrt S, Goulding CW. Differentiating the roles of Mycobacterium tuberculosis substrate binding proteins, FecB and FecB2, in iron uptake. PLoS Pathog 2023; 19:e1011650. [PMID: 37747938 PMCID: PMC10553834 DOI: 10.1371/journal.ppat.1011650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 10/05/2023] [Accepted: 08/31/2023] [Indexed: 09/27/2023] Open
Abstract
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, poses a great threat to human health. With the emergence of drug resistant Mtb strains, new therapeutics are desperately needed. As iron is critical to the growth and survival of Mtb, mechanisms through which Mtb acquires host iron represent attractive therapeutic targets. Mtb scavenges host iron via Mtb siderophore-dependent and heme iron uptake pathways. While multiple studies describe the import of heme and ferric-siderophores and the export of apo-siderophores across the inner membrane, little is known about their transport across the periplasm and cell-wall environments. Mtb FecB and FecB2 are predicted periplasmic binding proteins implicated in host iron acquisition; however, their precise roles are not well understood. This study sought to differentiate the roles FecB and FecB2 play in Mtb iron acquisition. The crystallographic structures of Mtb FecB and FecB2 were determined to 2.0 Å and 2.2 Å resolution, respectively, and show distinct ligand binding pockets. In vitro ligand binding experiments for FecB and FecB2 were performed with heme and bacterial siderophores from Mtb and other species, revealing that both FecB and FecB2 bind heme, while only FecB binds the Mtb sideophore ferric-carboxymycobactin (Fe-cMB). Subsequent structure-guided mutagenesis of FecB identified a single glutamate residue-Glu339-that significantly contributes to Fe-cMB binding. A role for FecB in the Mtb siderophore-mediated iron acquisition pathway was corroborated by Mycobacterium smegmatis and Mtb pull-down assays, which revealed interactions between FecB and members of the mycobacterial siderophore export and import machinery. Similarly, pull-down assays with FecB2 confirms its role in heme uptake revealing interactions with a potential inner membrane heme importer. Due to ligand preference and protein partners, our data suggest that Mtb FecB plays a role in siderophore-dependent iron and heme acquisition pathways; in addition, we confirm that Mtb FecB2 is involved in heme uptake.
Collapse
Affiliation(s)
- Rodger de Miranda
- Department of Molecular Biology & Biochemistry, University of California Irvine, Irvine, California, United States of America
| | - Bonnie J. Cuthbert
- Department of Molecular Biology & Biochemistry, University of California Irvine, Irvine, California, United States of America
| | - Thaís Klevorn
- Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America
| | - Alex Chao
- Department of Molecular Biology & Biochemistry, University of California Irvine, Irvine, California, United States of America
| | - Jessica Mendoza
- Department of Molecular Biology & Biochemistry, University of California Irvine, Irvine, California, United States of America
| | - Mark Arbing
- UCLA-DOE Institute, UCLA, Los Angeles, Calofornia, United States of America
| | - Paul J. Sieminski
- Department of Molecular Biology & Biochemistry, University of California Irvine, Irvine, California, United States of America
| | - Kadamba Papavinasasundaram
- Department of Microbiology and Physiological Systems, UMass Chan Medical School, Worcester, Massachusetts, United States of America
| | - Sumer Abdul-Hafiz
- Department of Molecular Biology & Biochemistry, University of California Irvine, Irvine, California, United States of America
| | - Sum Chan
- Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America
| | - Christopher M. Sassetti
- Department of Microbiology and Physiological Systems, UMass Chan Medical School, Worcester, Massachusetts, United States of America
| | - Sabine Ehrt
- Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America
| | - Celia W. Goulding
- Department of Molecular Biology & Biochemistry, University of California Irvine, Irvine, California, United States of America
- Department of Pharmaceutical Sciences, University of California Irvine, Irvine, Califiornia, United States of America
| |
Collapse
|
|
9
|
Shames SR. Eat or Be Eaten: Strategies Used by Legionella to Acquire Host-Derived Nutrients and Evade Lysosomal Degradation. Infect Immun 2023; 91:e0044122. [PMID: 36912646 PMCID: PMC10112212 DOI: 10.1128/iai.00441-22] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/14/2023] Open
Abstract
To replicate within host cells, bacterial pathogens must acquire host-derived nutrients while avoiding degradative antimicrobial pathways. Fundamental insights into bacterial pathogenicity have been revealed by bacteria of the genus Legionella, which naturally parasitize free-living protozoa by establishing a membrane-bound replicative niche termed the Legionella-containing vacuole (LCV). Biogenesis of the LCV and intracellular replication rely on rapid evasion of the endocytic pathway and acquisition of host-derived nutrients, much of which is mediated by bacterial effector proteins translocated into host cells by a Dot/Icm type IV secretion system. Billions of years of co-evolution with eukaryotic hosts and broad host tropism have resulted in expansion of the Legionella genome to accommodate a massive repertoire of effector proteins that promote LCV biogenesis, safeguard the LCV from endolysosomal maturation, and mediate the acquisition of host nutrients. This minireview is focused on the mechanisms by which an ancient intracellular pathogen leverages effector proteins and hijacks host cell biology to obtain essential host-derived nutrients and prevent lysosomal degradation.
Collapse
Affiliation(s)
- Stephanie R. Shames
- Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, Michigan, USA
| |
Collapse
|
|
10
|
Li B, Wu G, Yang X, Li Z, Albasher G, Alsultan N, Memon AA, Afridi HI. Correlation of endocrine disrupting chemicals with essential elements in biological samples of children (1-5 years) with different infectious diseases and impact on sustainable outdoor activities. ENVIRONMENTAL RESEARCH 2023; 229:115781. [PMID: 37076035 DOI: 10.1016/j.envres.2023.115781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 03/22/2023] [Accepted: 03/25/2023] [Indexed: 05/03/2023]
Abstract
Endocrine disrupting chemicals (EDCs) have been extensively explored due to their harmful effects on individual health and the environment by interfering with hormone activity and disrupting the endocrine system. However, their relationship with essential trace elements remains uncertain. This research aimed to investigate the possible correlation between essential trace elements and toxic metals, including cadmium (Cd), and lead (Pb) in children aged 1-5 years with various infectious diseases, including gastrointestinal disorders, typhoid fever, and pneumonia. The study was conducted on biological testing and specimen (scalp hair and whole blood) of diseased and non-diseased children of the same residential area and referent/control age-matched children from developed cities consuming domestically treated water. The media of biological samples were oxidized by an acid mixture before being analyzed by atomic absorption spectrophotometry. The accuracy and validity of the methodology were verified through accredited reference material from scalp hair and whole blood sample. The study results revealed that diseased children had lower mean values of essential trace elements (iron, copper, and zinc) in both scalp hair and blood, except for copper, which was found to be higher in blood samples of diseased children. This implies that the deficiency of essential residue and trace elements in children from rural areas who consume groundwater is linked to various infectious diseases. The study highlights the need for more human biomonitoring of EDCs to better comprehend their non-classical toxic properties and their concealed costs on human health. The findings suggest that exposure to EDCs could be associated with unfavorable health outcomes and emphasizes the need for future regulatory policies to minimize exposure and safeguard the health of current and forthcoming generations of children. Furthermore, the study highlights the implication of essential trace elements in maintaining good health and their potential correlation with toxic metals in the environment.
Collapse
Affiliation(s)
- Bo Li
- Physical Education Department, Xi'an University of Finance and Economics, 64 Xiaozhai E Rd, Yanta District, Xi'An, Shaanxi, China
| | - Guangliang Wu
- Physical Education Department, Renmin University of China, No. 59, Zhongguancun Street, Haidian District, Beijing, China.
| | - Xiaoguang Yang
- Physical Education Department, Xi'an University of Finance and Economics, 64 Xiaozhai E Rd, Yanta District, Xi'An, Shaanxi, China
| | - Zeyun Li
- Geography Section, School of Humanities, Universiti Sains Malaysia, Penang, Malaysia
| | - Gadah Albasher
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Nouf Alsultan
- Faculty of Medicine and Health Sciences, University of Nottingham, United Kingdom
| | - Aijaz Ahmed Memon
- National Center of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080, Pakistan
| | - Hassan Imran Afridi
- National Center of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080, Pakistan
| |
Collapse
|
|
11
|
Dao TH, Iverson A, Neville SL, Johnson MDL, McDevitt CA, Rosch JW. The role of CopA in Streptococcus pyogenes copper homeostasis and virulence. J Inorg Biochem 2023; 240:112122. [PMID: 36639322 PMCID: PMC10161136 DOI: 10.1016/j.jinorgbio.2023.112122] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 01/09/2023]
Abstract
Maintenance of intracellular metal homeostasis during interaction with host niches is critical to the success of bacterial pathogens. To prevent infection, the mammalian innate immune response employs metal-withholding and metal-intoxication mechanisms to limit bacterial propagation. The first-row transition metal ion copper serves critical roles at the host-pathogen interface and has been associated with antimicrobial activity since antiquity. Despite lacking any known copper-utilizing proteins, streptococci have been reported to accumulate significant levels of copper. Here, we report that loss of CopA, a copper-specific exporter, confers increased sensitivity to copper in Streptococcus pyogenes strain HSC5, with prolonged exposure to physiological levels of copper resulting in reduced viability during stationary phase cultivation. This defect in stationary phase survival was rescued by supplementation with exogeneous amino acids, indicating the pathogen had altered nutritional requirements during exposure to copper stress. Furthermore, S. pyogenes HSC5 ΔcopA was substantially attenuated during murine soft-tissue infection, demonstrating the importance of copper efflux at the host-pathogen interface. Collectively, these data indicate that copper can severely reduce the viability of stationary phase S. pyogenes and that active efflux mechanisms are required to survive copper stress in vitro and during infection.
Collapse
Affiliation(s)
- Tina H Dao
- St. Jude Children's Research Hospital, Department of Infectious Diseases, 262 Danny Thomas Place, Memphis, TN 38105, USA
| | - Amy Iverson
- St. Jude Children's Research Hospital, Department of Infectious Diseases, 262 Danny Thomas Place, Memphis, TN 38105, USA
| | - Stephanie L Neville
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia
| | - Michael D L Johnson
- St. Jude Children's Research Hospital, Department of Infectious Diseases, 262 Danny Thomas Place, Memphis, TN 38105, USA; Department of Immunobiology, BIO5 Institute, Valley Fever Center for Excellence, and Asthma and Airway Disease Research Center, University of Arizona College of Medicine - Tucson, Tucson, AZ 85724, USA
| | - Christopher A McDevitt
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia
| | - Jason W Rosch
- St. Jude Children's Research Hospital, Department of Infectious Diseases, 262 Danny Thomas Place, Memphis, TN 38105, USA.
| |
Collapse
|
|
12
|
Shisaka Y, Shoji O. Bridging the gap: Unveiling novel functions of a bacterial haem-acquisition protein capturing diverse synthetic porphyrinoids. Coord Chem Rev 2022. [DOI: 10.1016/j.ccr.2022.214793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
|
|
13
|
Orata FD, Hussain NAS, Liang KYH, Hu D, Boucher YF. Genomes of Vibrio metoecus co-isolated with Vibrio cholerae extend our understanding of differences between these closely related species. Gut Pathog 2022; 14:42. [PMID: 36404338 PMCID: PMC9677704 DOI: 10.1186/s13099-022-00516-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 11/04/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Vibrio cholerae, the causative agent of cholera, is a well-studied species, whereas Vibrio metoecus is a recently described close relative that is also associated with human infections. The availability of V. metoecus genomes provides further insight into its genetic differences from V. cholerae. Additionally, both species have been co-isolated from a cholera-free brackish coastal pond and have been suggested to interact with each other by horizontal gene transfer (HGT). RESULTS The genomes of 17 strains from each species were sequenced. All strains share a large core genome (2675 gene families) and very few genes are unique to each species (< 3% of the pan-genome of both species). This led to the identification of potential molecular markers-for nitrite reduction, as well as peptidase and rhodanese activities-to further distinguish V. metoecus from V. cholerae. Interspecies HGT events were inferred in 21% of the core genes and 45% of the accessory genes. A directional bias in gene transfer events was found in the core genome, where V. metoecus was a recipient of three times (75%) more genes from V. cholerae than it was a donor (25%). CONCLUSION V. metoecus was misclassified as an atypical variant of V. cholerae due to their resemblance in a majority of biochemical characteristics. More distinguishing phenotypic assays can be developed based on the discovery of potential gene markers to avoid any future misclassifications. Furthermore, differences in relative abundance or seasonality were observed between the species and could contribute to the bias in directionality of HGT.
Collapse
Affiliation(s)
- Fabini D. Orata
- grid.17089.370000 0001 2190 316XDepartment of Biological Sciences, University of Alberta, Edmonton, Alberta Canada ,grid.17089.370000 0001 2190 316XDepartment of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta Canada
| | - Nora A. S. Hussain
- grid.17089.370000 0001 2190 316XDepartment of Biological Sciences, University of Alberta, Edmonton, Alberta Canada
| | - Kevin Y. H. Liang
- grid.17089.370000 0001 2190 316XDepartment of Biological Sciences, University of Alberta, Edmonton, Alberta Canada ,grid.14709.3b0000 0004 1936 8649Department of Quantitative Life Sciences, McGill University, Montréal, Québec Canada ,grid.14709.3b0000 0004 1936 8649Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec Canada
| | - Dalong Hu
- grid.4280.e0000 0001 2180 6431Saw Swee Hock School of Public Health, National University of Singapore and National University Hospital System, Singapore, Singapore ,grid.4280.e0000 0001 2180 6431Singapore Centre for Environmental Life Sciences Engineering, National University of Singapore, Singapore, Singapore
| | - Yann F. Boucher
- grid.17089.370000 0001 2190 316XDepartment of Biological Sciences, University of Alberta, Edmonton, Alberta Canada ,grid.4280.e0000 0001 2180 6431Saw Swee Hock School of Public Health, National University of Singapore and National University Hospital System, Singapore, Singapore ,grid.4280.e0000 0001 2180 6431Singapore Centre for Environmental Life Sciences Engineering, National University of Singapore, Singapore, Singapore ,grid.4280.e0000 0001 2180 6431Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore and National University Hospital System, Singapore, Singapore
| |
Collapse
|
|
14
|
Kroniger T, Mehanny M, Schlüter R, Trautwein-Schult A, Köllner B, Becher D. Effect of Iron Limitation, Elevated Temperature, and Florfenicol on the Proteome and Vesiculation of the Fish Pathogen Aeromonas salmonicida. Microorganisms 2022; 10:microorganisms10091735. [PMID: 36144337 PMCID: PMC9503180 DOI: 10.3390/microorganisms10091735] [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: 06/30/2022] [Revised: 08/19/2022] [Accepted: 08/24/2022] [Indexed: 11/16/2022] Open
Abstract
We analyzed the proteomic response of the Gram-negative fish pathogen A. salmonicida to iron limitation, an elevated incubation temperature, and the antibiotic florfenicol. Proteins from different subcellular fractions (cytosol, inner membrane, outer membrane, extracellular and outer membrane vesicles) were enriched and analyzed. We identified several iron-regulated proteins that were not reported in the literature for A. salmonicida before. We could also show that hemolysin, an oxidative-stress-resistance chaperone, a putative hemin receptor, an M36 peptidase, and an uncharacterized protein were significantly higher in abundance not only under iron limitation but also with an elevated incubation temperature. This may indicate that these proteins involved in the infection process of A. salmonicida are induced by both factors. The analysis of the outer membrane vesicles (OMVs) with and without applied stresses revealed significant differences in the proteomes. OMVs were smaller and contained more cytoplasmic proteins after antibiotic treatment. After cultivation with low iron availability, several iron-regulated proteins were found in the OMVs, indicating that A. salmonicida OMVs potentially have a function in iron acquisition, as reported for other bacteria. The presence of iron-regulated transporters further indicates that OMVs obtained from ‘stressed’ bacteria might be suitable vaccine candidates that induce a protective anti-virulence immune response.
Collapse
Affiliation(s)
- Tobias Kroniger
- Institute of Microbiology, Department of Microbial Proteomics, Center for Functional Genomics of Microbes, University of Greifswald, 17489 Greifswald, Germany
| | - Mina Mehanny
- Helmholtz Institute for Pharmaceutical Research Saarland, 66123 Saarbrücken, Germany
- Department of Pharmacy, Saarland University, 66123 Saarbrücken, Germany
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt
| | - Rabea Schlüter
- Imaging Center of the Department of Biology, University of Greifswald, 17489 Greifswald, Germany
| | - Anke Trautwein-Schult
- Institute of Microbiology, Department of Microbial Proteomics, Center for Functional Genomics of Microbes, University of Greifswald, 17489 Greifswald, Germany
| | - Bernd Köllner
- Institute of Immunology, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany
| | - Dörte Becher
- Institute of Microbiology, Department of Microbial Proteomics, Center for Functional Genomics of Microbes, University of Greifswald, 17489 Greifswald, Germany
- Correspondence: ; Tel.: +49-3834-420-5903
| |
Collapse
|
|
15
|
Role of Iron in Aging Related Diseases. Antioxidants (Basel) 2022; 11:antiox11050865. [PMID: 35624729 PMCID: PMC9137504 DOI: 10.3390/antiox11050865] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/17/2022] [Accepted: 04/25/2022] [Indexed: 02/05/2023] Open
Abstract
Iron progressively accumulates with age and can be further exacerbated by dietary iron intake, genetic factors, and repeated blood transfusions. While iron plays a vital role in various physiological processes within the human body, its accumulation contributes to cellular aging in several species. In its free form, iron can initiate the formation of free radicals at a cellular level and contribute to systemic disorders. This is most evident in high iron conditions such as hereditary hemochromatosis, when accumulation of iron contributes to the development of arthritis, cirrhosis, or cardiomyopathy. A growing body of research has further identified iron’s contributory effects in neurodegenerative diseases, ocular disorders, cancer, diabetes, endocrine dysfunction, and cardiovascular diseases. Reducing iron levels by repeated phlebotomy, iron chelation, and dietary restriction are the common therapeutic considerations to prevent iron toxicity. Chelators such as deferoxamine, deferiprone, and deferasirox have become the standard of care in managing iron overload conditions with other potential applications in cancer and cardiotoxicity. In certain animal models, drugs with iron chelating ability have been found to promote health and even extend lifespan. As we further explore the role of iron in the aging process, iron chelators will likely play an increasingly important role in our health.
Collapse
|
|
16
|
Zinc Deficiency Interacts with Intestinal/Urogenital Parasites in the Pathway to Anemia in Preschool Children, Bengo–Angola. Nutrients 2022; 14:nu14071392. [PMID: 35406005 PMCID: PMC9002711 DOI: 10.3390/nu14071392] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/23/2022] [Accepted: 03/01/2022] [Indexed: 02/03/2023] Open
Abstract
In host organisms with normal micronutrient status, nutritional immunity is a strongly regulated response aiming at decreasing the progression and severity of infections. Zinc deficiency may disturb this balance, impairing immune responses to infections, which may indirectly increase infection-related anemia. Since zinc deficiency may associate directly with anemia, the role of infections is often overlooked. Herein, we investigated the participation of infections (or inflammation) in the causal pathway between zinc deficiency and anemia. This transversal study, conducted in 2015 in Bengo-Angola, enrolled 852 under-3-year-old children. Logistic regression models were used to investigate interaction and mediation effects, and significance was confirmed by the Sobel test. In sum, 6.8% of children had zinc deficiency, 45.9% had anemia, and 15.6% had at least one intestinal/urogenital parasite. Furthermore, we found (1) no evidence that inflammation mediates or interacts with zinc deficiency to cause anemia, and (2) zinc deficiency interacts with infections, significantly increasing the odds of anemia (OR: 13.26, p = 0.022). This interaction was stronger among children with iron deficiency anemia (OR: 46.66, p = 0.003). Our results suggest that zinc deficiency may impair the immune response to infections and/or that intestinal parasites could have developed mechanisms to avoid zinc-limited environments. Further studies are needed to corroborate these suggestions.
Collapse
|
|
17
|
Pan P, Wang X, Chen Y, Chen Q, Yang Y, Wei C, Cheng T, Wan H, Yu D. Effect of Hcp Iron Ion Regulation on the Interaction Between Acinetobacter baumannii With Human Pulmonary Alveolar Epithelial Cells and Biofilm Formation. Front Cell Infect Microbiol 2022; 12:761604. [PMID: 35281445 PMCID: PMC8905654 DOI: 10.3389/fcimb.2022.761604] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 01/31/2022] [Indexed: 11/15/2022] Open
Abstract
Acinetobacter baumannii is a type of bacterial nosocomial infection with severe drug resistance. Hemolysin co-regulated protein (Hcp) is a marker of activated type VI secretion system (T6SS), a key secretory system that promotes Gram-negative bacteria colonization, adhesion, and invasion of host cells. Hcp is also regulated by iron ions (Fe). In this study, an ATCC17978 hcp deletion strain (ATCC17978Δhcp), an hcp complement strain (ATCC17978Δhcp+), and an A. baumannii–green fluorescent protein (GFP) strain were constructed and used to investigate the role of hcp in bacterial adhesion to cells (human pulmonary alveolar epithelial cells (HPAEpiC)) and biofilm formation. Our results indicate that the inhibitory concentrations of the three A. baumannii strains (ATCC17978 wild type, ATCC17978Δhcp, and ATCC17978Δhcp+) were drug-sensitive strains. A. baumannii hcp gene and iron ions might be involved in promoting the formation of a biofilm and host–bacteria interaction. Iron ions affected the ability of A. baumannii to adhere to cells, as there was no significant difference in the bacterial numbers when assessing the adhesion of the three strains to HPAEpiC in the presence of iron ion concentrations of 0 μM (F = 3.1800, p = 0.1144), 25 μM (F = 2.067, p = 0.2075), 100 μM (F = 30.52, p = 0.0007), and 400 μM (F = 17.57, p = 0.0031). The three strains showed significant differences in their ability to adhere to HPAEpiC. The numbers of bacteria adhesion to HPAEpiC were ATCC17978Δhcp>ATCC17978Δhcp+>ATCC17978 in descending order. Hcp gene was positively regulated by iron ions in the bacteria–cells’ co-culture. It is speculated that the effect of iron ions on the interaction between A. baumannii and HPAEpiC might be related to the transport function of hcp and bacterial immune escape mechanisms.
Collapse
Affiliation(s)
- Ping Pan
- Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Medical Laboratory, Hangzhou Women’s Hospital, Hangzhou, China
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiaolei Wang
- Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yi Chen
- Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Medical Laboratory, Zhejiang Hospital, Hangzhou, China
| | - Qiong Chen
- Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yunxing Yang
- Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Chenxing Wei
- Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tongtong Cheng
- Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Haitong Wan
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- *Correspondence: Haitong Wan, ; Daojun Yu,
| | - Daojun Yu
- Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- *Correspondence: Haitong Wan, ; Daojun Yu,
| |
Collapse
|
|
18
|
Xue X, Caballero-Solares A, Hall JR, Umasuthan N, Kumar S, Jakob E, Skugor S, Hawes C, Santander J, Taylor RG, Rise ML. Transcriptome Profiling of Atlantic Salmon ( Salmo salar) Parr With Higher and Lower Pathogen Loads Following Piscirickettsia salmonis Infection. Front Immunol 2022; 12:789465. [PMID: 35035387 PMCID: PMC8758579 DOI: 10.3389/fimmu.2021.789465] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 12/03/2021] [Indexed: 12/29/2022] Open
Abstract
Salmonid rickettsial septicemia (SRS), caused by Piscirickettsia salmonis, is one of the most devastating diseases of salmonids. However, the transcriptomic responses of Atlantic salmon (Salmon salar) in freshwater to an EM-90-like isolate have not been explored. Here, we infected Atlantic salmon parr with an EM-90-like isolate and conducted time-course qPCR analyses of pathogen load and four biomarkers (campb, hampa, il8a, tlr5a) of innate immunity on the head kidney samples. Transcript expression of three of these genes (except hampa), as well as pathogen level, peaked at 21 days post-injection (DPI). Multivariate analyses of infected individuals at 21 DPI revealed two infection phenotypes [lower (L-SRS) and higher (H-SRS) infection level]. Five fish from each group (Control, L-SRS, and H-SRS) were selected for transcriptome profiling using a 44K salmonid microarray platform. We identified 1,636 and 3,076 differentially expressed probes (DEPs) in the L-SRS and H-SRS groups compared with the control group, respectively (FDR = 1%). Gene ontology term enrichment analyses of SRS-responsive genes revealed the activation of a large number of innate (e.g. “phagocytosis”, “defense response to bacterium”, “inflammatory response”) and adaptive (e.g. “regulation of T cell activation”, “antigen processing and presentation of exogenous antigen”) immune processes, while a small number of general physiological processes (e.g. “apoptotic process”, development and metabolism relevant) was enriched. Transcriptome results were confirmed by qPCR analyses of 42 microarray-identified transcripts. Furthermore, the comparison of individuals with differing levels of infection (H-SRS vs. L-SRS) generated insights into the biological processes possibly involved in disease resistance or susceptibility. This study demonstrated a low mortality (~30%) EM-90-like infection model and broadened the current understanding of molecular pathways underlying P. salmonis-triggered responses of Atlantic salmon, identifying biomarkers that may assist to diagnose and combat this pathogen.
Collapse
Affiliation(s)
- Xi Xue
- Department of Ocean Sciences, Memorial University of Newfoundland, St. John's, NL, Canada
| | | | - Jennifer R Hall
- Aquatic Research Cluster, CREAIT Network, Ocean Sciences Centre, Memorial University of Newfoundland, St. John's, NL, Canada
| | | | - Surendra Kumar
- Department of Ocean Sciences, Memorial University of Newfoundland, St. John's, NL, Canada
| | - Eva Jakob
- Cargill Innovation Centre - Colaco, Colaco, Chile
| | - Stanko Skugor
- Cargill Aqua Nutrition, Cargill, Sea Lice Research Center (SLRC), Sandnes, Norway
| | | | - Javier Santander
- Marine Microbial Pathogenesis and Vaccinology Lab, Department of Ocean Sciences, Memorial University of Newfoundland, St. John's, NL, Canada
| | - Richard G Taylor
- Cargill Animal Nutrition and Health, Elk River, MN, United States
| | - Matthew L Rise
- Department of Ocean Sciences, Memorial University of Newfoundland, St. John's, NL, Canada
| |
Collapse
|
|
19
|
Ginefra P, Carrasco Hope H, Spagna M, Zecchillo A, Vannini N. Ionic Regulation of T-Cell Function and Anti-Tumour Immunity. Int J Mol Sci 2021; 22:ijms222413668. [PMID: 34948472 PMCID: PMC8705279 DOI: 10.3390/ijms222413668] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/15/2021] [Accepted: 12/17/2021] [Indexed: 12/02/2022] Open
Abstract
The capacity of T cells to identify and kill cancer cells has become a central pillar of immune-based cancer therapies. However, T cells are characterized by a dysfunctional state in most tumours. A major obstacle for proper T-cell function is the metabolic constraints posed by the tumour microenvironment (TME). In the TME, T cells compete with cancer cells for macronutrients (sugar, proteins, and lipid) and micronutrients (vitamins and minerals/ions). While the role of macronutrients in T-cell activation and function is well characterized, the contribution of micronutrients and especially ions in anti-tumour T-cell activities is still under investigation. Notably, ions are important for most of the signalling pathways regulating T-cell anti-tumour function. In this review, we discuss the role of six biologically relevant ions in T-cell function and in anti-tumour immunity, elucidating potential strategies to adopt to improve immunotherapy via modulation of ion metabolism.
Collapse
|
|
20
|
Murphy T, Phan K, Irvine KN, Lean D. The Role of Micronutrients and Toxic Metals in the Management of Epidemics in Cambodia. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:11446. [PMID: 34769963 PMCID: PMC8582812 DOI: 10.3390/ijerph182111446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 10/11/2021] [Accepted: 10/28/2021] [Indexed: 11/16/2022]
Abstract
The illegal trade of wildlife in SE Asia has been identified as the likely cause of the COVID-19 pandemic. We reviewed 198 papers on the current COVID pandemic in Cambodia, diseases such as avian influenza and Nipah virus, most likely to develop into a new pandemic in Cambodia, and common features of disease that require mitigation. Artisanal goldmining uses pure mercury in the areas where wildlife is smuggled to China. Moreover, 30-40% of Cambodians are zinc deficient. High levels of arsenic in irrigation water (>1000 µg/L) are associated with very low levels of zinc in rice (5 µg/g) and rice is the primary staple food for the region. Brown rice from nine of 15 paddy fields in the arsenic zone of Cambodia had double the new guidelines of 100 µg/kg inorganic arsenic for children's food in the EU and USA. The combination of deficiencies of essential micronutrients like zinc and pervasive presence of arsenic and mercury has the potential to compromise the immunity of many Cambodians. Innovative solutions are suggested to improve micronutrient nutrition. Toxins that suppress the immune system must be better managed to reduce the virulence of pathogens. Cambodia was not likely the source of the COVID-19 but does have problems that could result in a new pandemic.
Collapse
Affiliation(s)
- Thomas Murphy
- Faculty of Science and Technology, International University, Phnom Penh 12000, Cambodia;
| | - Kongkea Phan
- Faculty of Science and Technology, International University, Phnom Penh 12000, Cambodia;
| | - Kim Neil Irvine
- Faculty of Architecture & Planning, Rangsit Campus, Thammasat University, Khlong Nueng 12121, Thailand;
| | - David Lean
- Lean Environmental, Apsley, ON K0L1A0, Canada;
| |
Collapse
|
|
21
|
Khan N, Halcrow PW, Lakpa LK, Rehan M, Chen X, Geiger JD. Endolysosome iron restricts Tat-mediated HIV-1 LTR transactivation by increasing HIV-1 Tat oligomerization and β-catenin expression. J Neurovirol 2021; 27:755-773. [PMID: 34550543 PMCID: PMC8602775 DOI: 10.1007/s13365-021-01016-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 08/06/2021] [Accepted: 08/24/2021] [Indexed: 12/31/2022]
Abstract
HIV-1 transactivator of transcription (Tat) protein is required for HIV-1 replication, and it has been implicated in the pathogenesis of HIV-1-associated neurocognitive disorder (HAND). HIV-1 Tat can enter cells via receptor-mediated endocytosis where it can reside in endolysosomes; upon its escape from these acidic organelles, HIV-1 Tat can enter the cytosol and nucleus where it activates the HIV-1 LTR promoter. Although it is known that HIV-1 replication is affected by the iron status of people living with HIV-1 (PLWH), very little is known about how iron affects HIV-1 Tat activation of the HIV-1 LTR promoter. Because HIV-1 proteins de-acidify endolysosomes and endolysosome de-acidification affects subcellular levels and actions of iron, we tested the hypothesis that the endolysosome pool of iron is sufficient to affect Tat-induced HIV-1 LTR transactivation. Ferric (Fe3+) and ferrous (Fe2+) iron both restricted Tat-mediated HIV-1 LTR transactivation. Chelation of endolysosome iron with deferoxamine (DFO) and 2-2 bipyridyl, but not chelation of cytosolic iron with deferiprone and deferasirox, significantly enhanced Tat-mediated HIV-1 LTR transactivation. In the presence of iron, HIV-1 Tat increasingly oligomerized and DFO prevented the oligomerization. DFO also reduced protein expression levels of the HIV-1 restriction agent beta-catenin in the cytosol and nucleus. These findings suggest that DFO increases HIV-1 LTR transactivation by increasing levels of the more active dimeric form of Tat relative to the less active oligomerized form of Tat, increasing the escape of dimeric Tat from endolysosomes, and/or reducing beta-catenin protein expression levels. Thus, intracellular iron might play a significant role in regulating HIV-1 replication, and these findings raise cautionary notes for chelation therapies in PLWH.
Collapse
Affiliation(s)
- Nabab Khan
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA
| | - Peter W Halcrow
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA
| | - Leo K Lakpa
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA
| | - Mohd Rehan
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
| | - Xuesong Chen
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA
| | - Jonathan D Geiger
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
| |
Collapse
|
|
22
|
Vatlin AA, Shitikov EA, Shahbaaz M, Bespiatykh DA, Klimina KM, Christoffels A, Danilenko VN, Maslov DA. Transcriptomic Profile of Mycobacterium smegmatis in Response to an Imidazo[1,2- b][1,2,4,5]tetrazine Reveals Its Possible Impact on Iron Metabolism. Front Microbiol 2021; 12:724042. [PMID: 34421882 PMCID: PMC8371482 DOI: 10.3389/fmicb.2021.724042] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 07/14/2021] [Indexed: 12/03/2022] Open
Abstract
Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex bacteria, is one of the most pressing health problems. The development of new drugs and new therapeutic regimens effective against the pathogen is one of the greatest challenges in the way of tuberculosis control. Imidazo[1,2-b][1,2,4,5]tetrazines have shown promising activity against M. tuberculosis and M. smegmatis strains. Mutations in MSMEG_1380 lead to mmpS5–mmpL5 operon overexpression, which provides M. smegmatis with efflux-mediated resistance to imidazo[1,2-b][1,2,4,5]tetrazines, but the exact mechanism of action of these compounds remains unknown. To assess the mode of action of imidazo[1,2-b][1,2,4,5]tetrazines, we analyzed the transcriptomic response of M. smegmatis to three different concentrations of 3a compound: 1/8×, 1/4×, and 1/2× MIC. Six groups of genes responsible for siderophore synthesis and transport were upregulated in a dose-dependent manner, while virtual docking revealed proteins involved in siderophore synthesis as possible targets for 3a. Thus, we suggest that imidazo[1,2-b][1,2,4,5]tetrazines may affect mycobacterial iron metabolism.
Collapse
Affiliation(s)
- Aleksey A Vatlin
- Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics Russian Academy of Sciences, Moscow, Russia.,Peoples' Friendship University of Russia (RUDN University), Moscow, Russia
| | - Egor A Shitikov
- Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia
| | - Mohd Shahbaaz
- South Africa Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Cape Town, South Africa
| | - Dmitry A Bespiatykh
- Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia
| | - Ksenia M Klimina
- Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics Russian Academy of Sciences, Moscow, Russia.,Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia
| | - Alan Christoffels
- South Africa Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Cape Town, South Africa
| | - Valery N Danilenko
- Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics Russian Academy of Sciences, Moscow, Russia
| | - Dmitry A Maslov
- Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics Russian Academy of Sciences, Moscow, Russia
| |
Collapse
|
|
23
|
Artym J, Zimecki M, Kruzel ML. Lactoferrin for Prevention and Treatment of Anemia and Inflammation in Pregnant Women: A Comprehensive Review. Biomedicines 2021; 9:898. [PMID: 34440102 PMCID: PMC8389615 DOI: 10.3390/biomedicines9080898] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/19/2021] [Accepted: 07/22/2021] [Indexed: 01/14/2023] Open
Abstract
Pregnancy is a physiological state that demands higher level of nutrients, including vitamins and minerals, for the growth and maintenance of the fetus. Iron deficiency is a part of most common diet deficiencies in pregnancy and has high clinical significance leading to the development of syderopenic anemia and its consequences for mother and child, such as higher risk of perinatal death, susceptibility to infection, intra-uteral growth inhibition, prematurity and low birth weight. Hence, iron supplementation is recommended for pregnant women; however dietary intake of iron from most commercially available formulas is often insufficient due to iron-poor bioavailability, or have undesired side-effects in the gastrointestinal tract, resulting in a discouraging and distrustful attitude to such treatment. The results of numerous studies indicate that diet supplementation with lactoferrin (LTF), an iron-binding protein, may be advantageous in prophylaxis and treatment of iron deficiency anemia. LTF, administered orally, normalizes iron homeostasis, not only by facilitating iron absorption, but also by inhibiting inflammatory processes responsible for anemia of chronic diseases, characterized by a functional iron deficit for physiological processes. LTF also protects against infections and inflammatory complications, caused by diagnostic surgical interventions in pregnant women. Beneficial, multidirectional actions of LTF during pregnancy encompass, in addition, inhibition of oxidative stress, normalization of intestine and genital tract microbiota and carbohydrate-lipid metabolism, protection of intestine barrier function, promotion of wound healing, as well as hypotensive, analgesic and antistress actions. Bovine lactoferrin (BLTF) is readily available on the nutritional market and generally recognized as safe (GRAS) for use in human diet.
Collapse
Affiliation(s)
- Jolanta Artym
- Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12 Str., 53-112 Wrocław, Poland;
| | - Michał Zimecki
- Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12 Str., 53-112 Wrocław, Poland;
| | - Marian L. Kruzel
- Department of Integrative Biology and Pharmacology, McGovern Medical School at Houston, University of Texas, 25 7505 Fannin Str., Third Floor 313, Houston, TX 77054, USA;
| |
Collapse
|
|
24
|
He L, Zhu D, Liang X, Li Y, Liao L, Yang C, Huang R, Zhu Z, Wang Y. Multi-Omics Sequencing Provides Insights Into Age-Dependent Susceptibility of Grass Carp ( Ctenopharyngodon idellus) to Reovirus. Front Immunol 2021; 12:694965. [PMID: 34220856 PMCID: PMC8247658 DOI: 10.3389/fimmu.2021.694965] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 05/18/2021] [Indexed: 12/21/2022] Open
Abstract
Grass carp (Ctenopharyngodon idellus) is an important aquaculture species in China that is affected by serious diseases, especially hemorrhagic disease caused by grass carp reovirus (GCRV). Grass carp have previously shown age-dependent susceptibility to GCRV, however, the mechanism by which this occurs remains poorly understood. Therefore, we performed transcriptome and metabolome sequencing on five-month-old (FMO) and three-year-old (TYO) grass carp to identify the potential mechanism. Viral challenge experiments showed that FMO fish were susceptible, whereas TYO fish were resistant to GCRV. RNA-seq showed that the genes involved in immune response, antigen presentation, and phagocytosis were significantly upregulated in TYO fish before the GCRV infection and at the early stage of infection. Metabolome sequencing showed that most metabolites were upregulated in TYO fish and downregulated in FMO fish after virus infection. Intragroup analysis showed that arachidonic acid metabolism was the most significantly upregulated pathway in TYO fish, whereas choline metabolism in cancer and glycerophospholispid metabolism were significantly downregulated in FMO fish after virus infection. Intergroup comparison revealed that metabolites from carbohydrate, amino acid, glycerophospholipid, and nucleotide metabolism were upregulated in TYO fish when compared with FMO fish. Moreover, the significantly differentially expressed metabolites showed antiviral effects both in vivo and in vitro. Based on these results, we concluded that the immune system and host biosynthesis and metabolism, can explain the age-dependent viral susceptibility in grass carp.
Collapse
Affiliation(s)
- Libo He
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.,College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Denghui Zhu
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.,College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Xinyu Liang
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.,College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Yongming Li
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China
| | - Lanjie Liao
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China
| | - Cheng Yang
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China
| | - Rong Huang
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China
| | - Zuoyan Zhu
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China
| | - Yaping Wang
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.,Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, China
| |
Collapse
|
|
25
|
Ebrahimzadeh-Attari V, Panahi G, Hebert JR, Ostadrahimi A, Saghafi-Asl M, Lotfi-Yaghin N, Baradaran B. Nutritional approach for increasing public health during pandemic of COVID-19: A comprehensive review of antiviral nutrients and nutraceuticals. Health Promot Perspect 2021; 11:119-136. [PMID: 34195036 PMCID: PMC8233676 DOI: 10.34172/hpp.2021.17] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 02/03/2021] [Indexed: 12/15/2022] Open
Abstract
Background: The novel coronavirus (COVID-19) is considered as the most life-threatening pandemic disease during the last decade. The individual nutritional status, though usually ignored in the management of COVID-19, plays a critical role in the immune function and pathogenesis of infection. Accordingly, the present review article aimed to report the effects of nutrients and nutraceuticals on respiratory viral infections including COVID-19, with a focus on their mechanisms of action. Methods: Studies were identified via systematic searches of the databases including PubMed/ MEDLINE, ScienceDirect, Scopus, and Google Scholar from 2000 until April 2020, using keywords. All relevant clinical and experimental studies published in English were included. Results: Protein-energy malnutrition (PEM) is common in severe respiratory infections and should be considered in the management of COVID-19 patients. On the other hand, obesity can be accompanied by decreasing the host immunity. Therefore, increasing physical activity at home and a slight caloric restriction with adequate intake of micronutrients and nutraceuticals are simple aids to boost host immunity and decrease the clinical manifestations of COVID-19. Conclusion: The most important nutrients which can be considered for COVID-19 management are vitamin D, vitamin C, vitamin A, folate, zinc, and probiotics. Their adequacy should be provided through dietary intake or appropriate supplementation. Moreover, adequate intake of some other dietary agents including vitamin E, magnesium, selenium, alpha linolenic acid and phytochemicals are required to maintain the host immunity.
Collapse
Affiliation(s)
| | - Ghodratollah Panahi
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - James R. Hebert
- Department of Epidemiology & Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA
- Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA
| | - Alireza Ostadrahimi
- Nutrition Research Center, Department of Clinical Nutrition, Faculty of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Saghafi-Asl
- Nutrition Research Center, Department of Clinical Nutrition, Faculty of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Lotfi-Yaghin
- Student Research Committee, Department of Clinical Nutrition, Faculty of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
|
26
|
Klenotic PA, Moseng MA, Morgan CE, Yu EW. Structural and Functional Diversity of Resistance-Nodulation-Cell Division Transporters. Chem Rev 2021; 121:5378-5416. [PMID: 33211490 PMCID: PMC8119314 DOI: 10.1021/acs.chemrev.0c00621] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Multidrug resistant (MDR) bacteria are a global threat with many common infections becoming increasingly difficult to eliminate. While significant effort has gone into the development of potent biocides, the effectiveness of many first-line antibiotics has been diminished due to adaptive resistance mechanisms. Bacterial membrane proteins belonging to the resistance-nodulation-cell division (RND) superfamily play significant roles in mediating bacterial resistance to antimicrobials. They participate in multidrug efflux and cell wall biogenesis to transform bacterial pathogens into "superbugs" that are resistant even to last resort antibiotics. In this review, we summarize the RND superfamily of efflux transporters with a primary focus on the assembly and function of the inner membrane pumps. These pumps are critical for extrusion of antibiotics from the cell as well as the transport of lipid moieties to the outer membrane to establish membrane rigidity and stability. We analyze recently solved structures of bacterial inner membrane efflux pumps as to how they bind and transport their substrates. Our cumulative data indicate that these RND membrane proteins are able to utilize different oligomerization states to achieve particular activities, including forming MDR pumps and cell wall remodeling machineries, to ensure bacterial survival. This mechanistic insight, combined with simulated docking techniques, allows for the design and optimization of new efflux pump inhibitors to more effectively treat infections that today are difficult or impossible to cure.
Collapse
Affiliation(s)
- Philip A. Klenotic
- Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland OH 44106, USA
| | - Mitchell A. Moseng
- Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland OH 44106, USA
| | - Christopher E. Morgan
- Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland OH 44106, USA
| | - Edward W. Yu
- Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland OH 44106, USA
| |
Collapse
|
|
27
|
Cunrath O, Palmer JD. An overview of Salmonella enterica metal homeostasis pathways during infection. ACTA ACUST UNITED AC 2021; 2:uqab001. [PMID: 34250489 PMCID: PMC8264917 DOI: 10.1093/femsml/uqab001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 03/19/2021] [Indexed: 12/14/2022]
Abstract
Nutritional immunity is a powerful strategy at the core of the battlefield between host survival and pathogen proliferation. A host can prevent pathogens from accessing biological metals such as Mg, Fe, Zn, Mn, Cu, Co or Ni, or actively intoxicate them with metal overload. While the importance of metal homeostasis for the enteric pathogen Salmonella enterica Typhimurium was demonstrated many decades ago, inconsistent results across various mouse models, diverse Salmonella genotypes, and differing infection routes challenge aspects of our understanding of this phenomenon. With expanding access to CRISPR-Cas9 for host genome manipulation, it is now pertinent to re-visit past results in the context of specific mouse models, identify gaps and incongruities in current knowledge landscape of Salmonella homeostasis, and recommend a straight path forward towards a more universal understanding of this historic host-microbe relationship.
Collapse
Affiliation(s)
- Olivier Cunrath
- Department of Zoology, University of Oxford, Zoology Research and Administration Building, 11a Mansfield Rd, Oxford, UK OX1 3SZ
| | - Jacob D Palmer
- Department of Zoology, University of Oxford, Zoology Research and Administration Building, 11a Mansfield Rd, Oxford, UK OX1 3SZ
| |
Collapse
|
|
28
|
Cometta S, Bock N, Suresh S, Dargaville TR, Hutmacher DW. Antibacterial Albumin-Tannic Acid Coatings for Scaffold-Guided Breast Reconstruction. Front Bioeng Biotechnol 2021; 9:638577. [PMID: 33869154 PMCID: PMC8044405 DOI: 10.3389/fbioe.2021.638577] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 03/08/2021] [Indexed: 12/15/2022] Open
Abstract
Infection is the major cause of morbidity after breast implant surgery. Biodegradable medical-grade polycaprolactone (mPCL) scaffolds designed and rooted in evidence-based research offer a promising alternative to overcome the limitations of routinely used silicone implants for breast reconstruction. Nevertheless, as with any implant, biodegradable scaffolds are susceptible to bacterial infection too, especially as bacteria can rapidly colonize the biomaterial surface and form biofilms. Biofilm-related infections are notoriously challenging to treat and can lead to chronic infection and persisting inflammation of surrounding tissue. To date, no clinical solution that allows to efficiently prevent bacterial infection while promoting correct implant integration, has been developed. In this study, we demonstrated for the first time, to our knowledge that the physical immobilization of 1 and 5% human serum albumin (HSA) onto the surface of 3D printed macro- and microporous mPCL scaffolds, resulted in a reduction of Staphylococcus aureus colonization by 71.7 ± 13.6% and 54.3 ± 12.8%, respectively. Notably, when treatment of scaffolds with HSA was followed by tannic acid (TA) crosslinking/stabilization, uniform and stable coatings with improved antibacterial activity were obtained. The HSA/TA-coated scaffolds were shown to be stable when incubated at physiological conditions in cell culture media for 7 days. Moreover, they were capable of inhibiting the growth of S. aureus and Pseudomonas aeruginosa, two most commonly found bacteria in breast implant infections. Most importantly, 1%HSA/10%TA- and 5%HSA/1%TA-coated scaffolds were able to reduce S. aureus colonization on the mPCL surface, by 99.8 ± 0.1% and 98.8 ± 0.6%, respectively, in comparison to the non-coated control specimens. This system offers a new biomaterial strategy to effectively translate the prevention of biofilm-related infections on implant surfaces without relying on the use of prophylactic antibiotic treatment.
Collapse
Affiliation(s)
- Silvia Cometta
- Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.,School of Mechanical, Medical and Process Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane, QLD, Australia
| | - Nathalie Bock
- Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.,Translational Research Institute, Brisbane, QLD, Australia.,School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia
| | - Sinduja Suresh
- Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.,School of Mechanical, Medical and Process Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane, QLD, Australia.,ARC Industrial Transformation Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing, Queensland University of Technology, Brisbane, QLD, Australia
| | - Tim R Dargaville
- School of Chemistry and Physics, Science and Engineering Faculty, Queensland University of Technology, Brisbane, QLD, Australia
| | - Dietmar W Hutmacher
- Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.,School of Mechanical, Medical and Process Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane, QLD, Australia.,ARC Industrial Transformation Training Centre in Additive Biomanufacturing, Queensland University of Technology, Brisbane, QLD, Australia
| |
Collapse
|
|
29
|
Anemia in preschool children from Angola: a review of the evidence. Porto Biomed J 2020; 5:e60. [PMID: 33299941 PMCID: PMC7722406 DOI: 10.1097/j.pbj.0000000000000060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 01/06/2020] [Indexed: 11/26/2022] Open
Abstract
Angola is one of the southern African countries with the highest prevalence of anemia, and despite the high geographic heterogeneity of its distribution across the country, it was reported to be indicative of a severe public health problem in some areas, mainly in children. Despite the relevance of this condition in the country there is still an important gap regarding scientific evidences and knowledge systematization in the indexed literature, that could be used to inform and optimize national public health policies willing to address it. Furthermore, the changes in anemia epidemiology among African preschool children and the late updates in nutrition-specific and nutrition-sensitive preventive strategies in the continent are of imperative relevance, as they could contribute to design context-specific national approaches to reduce anemia's morbidity and mortality. In this study we intent to perform a systematic review regarding the sparse evidence available on the country regarding the prevalence of anemia, its associated factors, the prevention, and/or control strategies with potential to reduce anemia that were implemented, and to discuss interventions targeting infections and/or nutrition conducted in other African countries.
Collapse
|
|
30
|
Sullivan KE, Mylniczenko ND, Nelson SE, Coffin B, Lavin SR. Practical Management of Iron Overload Disorder (IOD) in Black Rhinoceros (BR; Diceros bicornis). Animals (Basel) 2020; 10:ani10111991. [PMID: 33138144 PMCID: PMC7692874 DOI: 10.3390/ani10111991] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 10/23/2020] [Accepted: 10/26/2020] [Indexed: 12/13/2022] Open
Abstract
Simple Summary Black rhinoceros under human care are predisposed to Iron Overload Disorder that is unlike the hereditary condition seen in humans. We aim to address the black rhino caretaker community at multiple perspectives (keeper, curator, veterinarian, nutritionist, veterinary technician, and researcher) to describe approaches to Iron Overload Disorder in black rhinos and share learnings. This report includes sections on (1) background on how iron functions in comparative species and how Iron Overload Disorder appears to work in black rhinos, (2) practical recommendations for known diagnostics, (3) a brief review of current investigations on inflammatory and other potential biomarkers, (4) nutrition knowledge and advice as prevention, and (5) an overview of treatment options including information on chelation and details on performing large volume voluntary phlebotomy. The aim is to use evidence to support the successful management of this disorder to ensure optimal animal health, welfare, and longevity for a sustainable black rhinoceros population. Abstract Critically endangered black rhinoceros (BR) under human care are predisposed to non-hemochromatosis Iron Overload Disorder (IOD). Over the last 30 years, BR have been documented with diseases that have either been induced by or exacerbated by IOD, prompting significant efforts to investigate and address this disorder. IOD is a multi-factorial chronic disease process requiring an evidence-based and integrative long-term approach. While research continues to elucidate the complexities of iron absorption, metabolism, and dysregulation in this species, preventive treatments are recommended and explained herein. The aim of this report is to highlight the accumulated evidence in nutrition, clinical medicine, and behavioral husbandry supporting the successful management of this disorder to ensure optimal animal health, welfare, and longevity for a sustainable black rhinoceros population.
Collapse
|
|
31
|
Nizamani P, Afridi HI, Kazi TG, Talpur FN, Baig JA. Essential trace elemental levels (zinc, iron and copper) in the biological samples of smoker referent and pulmonary tuberculosis patients. Toxicol Rep 2019; 6:1230-1239. [PMID: 31799123 PMCID: PMC6883299 DOI: 10.1016/j.toxrep.2019.11.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Revised: 11/10/2019] [Accepted: 11/13/2019] [Indexed: 01/16/2023] Open
Abstract
Smoking is linked with tuberculosis recurrence. Pakistan has not only high TB number of TB cases (fifth) but also high level of multidrug-resistant TB (fourth) in the world. Cu/Zn ratio was also considerably greater in all biological samples of TB patients as compared to the control group. The analysis the levels of the elements, {Fe, Cu, Zn and Cu/Zn ratio} may help the studies on the development of TB disease. Tuberculosis is one of the major causes of illnesses and deaths throughout world particularly in Asia. Smoking is linked with tuberculosis recurrence and its mortality and may influence bacteriological conversion, clinical symptoms and treatment outcome. The aim of current study was to estimate association among essential trace elements {zinc (Zn), iron (Fe) and copper (Cu)} in human biological samples particularly blood, serum, scalp hair, saliva, sputum, and nasal fluid of smoking and nonsmoking pulmonary tuberculosis patients (n = 165, age ranged 16–35 years) residents of Hyderabad, Pakistan. The biological samples of age matched healthy controls were chosen as referents of both genders (n = 171) for the comparison purpose. The human biological samples were wet digested in microwave oven by 65 % HNO3 and 30 % H2O2 with (2:1) ratio. The concentrations of elements in acid digested samples were determined by atomic absorption spectrometry. The average zinc and iron concentration was lower, while level of copper was higher in the biological samples of pulmonary Tuberculosis patients as compared to referent subjects (p < .001). It was also concluded as a result of Zn and Fe deficiency combined with high contact of copper due to smoking of tobacco can be synergistic with the risk factors related with pulmonary tuberculosis.
Collapse
Affiliation(s)
- Palwasha Nizamani
- National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080, Pakistan
| | - Hassan Imran Afridi
- National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080, Pakistan
| | - Tasneem Gul Kazi
- National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080, Pakistan
| | - Farah Naz Talpur
- National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080, Pakistan
| | - Jameel Ahmed Baig
- National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080, Pakistan
| |
Collapse
|
|
32
|
Denholm SJ, Sneddon AA, McNeilly TN, Bashir S, Mitchell MC, Wall E. Phenotypic and genetic analysis of milk and serum element concentrations in dairy cows. J Dairy Sci 2019; 102:11180-11192. [PMID: 31587908 DOI: 10.3168/jds.2019-16960] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 08/20/2019] [Indexed: 11/19/2022]
Abstract
Enhancing micronutrient (i.e., mineral and vitamin) concentrations within milk and serum from dairy cows is important for both the health of the cow and the nutritive value of the milk for human consumption. However, a good understanding of the genetics underlying the micronutrient content in dairy cattle is needed to facilitate such enhancements through feeding or breeding practices. In this study, milk (n = 950) and serum (n = 766) samples were collected from Holstein-Friesian dairy cows (n = 479) on 19 occasions over a 59-mo period and analyzed for concentrations of important elements. Additionally, a subset of 256 milk samples was analyzed for concentrations of vitamin B12. Cows belonged to 2 genetic lines (average and highest genetic merit for milk fat plus protein yield) and were assigned to 1 of 2 diets based on either a by-product or homegrown ration. Univariate models accounting for repeated records were used to analyze element and vitamin B12 data and investigate the effect of genotype and feeding system as well as derive estimates of variance components and genetic parameters. Bivariate models were used to study correlations both within and between milk and serum. Only concentrations of Hg in milk were seen to be affected by genotype, with higher concentrations in cows with high genetic merit. In contrast, element concentrations were influenced by feeding system such that cows fed the homegrown diet had increased milk concentrations of Ca, Cu, I, Mn, Mo, P, and K and increased serum concentrations of Cd, Cu, Fe, Mo, and V. Cows on the by-product diet had increased milk concentrations of Mg, Se, and Na and increased serum concentrations of P and Se. Heritability (h2) estimates were obtained for 6 milk and 4 serum elements, including Mg (h2milk = 0.30), K (h2serum = 0.18), Ca (h2milk = 0.20; h2serum = 0.12), Mn (h2milk = 0.14), Cu (h2serum = 0.22), Zn (h2milk = 0.24), Se (h2milk = 0.15; h2serum = 0.10), and Mo (h2milk = 0.19). Significant estimates of repeatability were observed in all milk and serum quantity elements (Na, Mg, P, K, and Ca) as well as 5 milk and 7 serum trace elements. Only K in milk and serum was found to have a significant positive genetic and phenotypic correlation (0.52 and 0.22, respectively). Significant phenotypic associations were noted between milk and serum Ca (0.17), Mo (0.19), and Na (-0.79). Additional multivariate analyses between measures within sample type (i.e., milk or serum) revealed significant positive associations, both phenotypic and genetic, between some of the elements. In milk, Se was genetically correlated with Ca (0.63), Mg (0.59), Mn (0.40), P (0.53), and Zn (0.52), whereas in serum, V showed strong genetic associations with Cd (0.71), Ca (0.53), Mn (0.63), Mo (0.57), P (0.42), K (0.45), and Hg (-0.44). These results provide evidence that element concentrations in milk and blood of dairy cows are significantly influenced by both diet and genetics and demonstrate the potential for genetic selection and dietary manipulation to alter nutrient concentration to improve both cow health and the healthfulness of milk for human consumption.
Collapse
Affiliation(s)
- Scott J Denholm
- Animal and Veterinary Sciences, Scotland's Rural College, Easter Bush, Midlothian, United Kingdom, EH25 9RG.
| | - Alan A Sneddon
- The Rowett Institute, University of Aberdeen, Aberdeen, United Kingdom, AB25 2ZD
| | - Tom N McNeilly
- Moredun Research Institute, Pentlands Science Park, Midlothian, United Kingdom, EH26 0PZ
| | - Shabina Bashir
- The Rowett Institute, University of Aberdeen, Aberdeen, United Kingdom, AB25 2ZD
| | - Mairi C Mitchell
- Moredun Research Institute, Pentlands Science Park, Midlothian, United Kingdom, EH26 0PZ
| | - Eileen Wall
- Animal and Veterinary Sciences, Scotland's Rural College, Easter Bush, Midlothian, United Kingdom, EH25 9RG
| |
Collapse
|
|
33
|
Alam I, Almajwal AM, Alam W, Alam I, Ullah N, Abulmeaaty M, Razak S, Khan S, Pawelec G, Paracha PI. The immune-nutrition interplay in aging – facts and controversies. ACTA ACUST UNITED AC 2019. [DOI: 10.3233/nha-170034] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Iftikhar Alam
- Department of Community Health Sciences, Clinical Nutrition Program, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
- Department of Human Nutrition & Dietetics, Bacha Khan University Charsadda, Charsadda, Khyber Pakhtunkhwa, Pakistan
- Tübingen Ageing and Tumour Immunology Group, Zentrum für Medizinische Forschung, University of Tübingen, Tübingen, Germany
| | - Ali M. Almajwal
- Department of Community Health Sciences, Clinical Nutrition Program, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Wajid Alam
- Oral and Maxillofacial Surgery, Khyber Colleg of Dentistry, KPK, Peshawar, Pakistan
| | - Ibrar Alam
- Department of Biotechnology, Bacha Khan University Charsadda, Charsadda, Khyber Pakhtunkhwa, Pakistan
| | - Niamat Ullah
- Department of Human Nutrition, The Agriculture University Peshawar, Khyber Pakhtunkhwa, Pakistan
| | - Mahmoud Abulmeaaty
- Department of Community Health Sciences, Clinical Nutrition Program, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Suhail Razak
- Department of Community Health Sciences, Clinical Nutrition Program, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Saleem Khan
- Department of Human Nutrition, The Agriculture University Peshawar, Khyber Pakhtunkhwa, Pakistan
| | - Graham Pawelec
- Tübingen Ageing and Tumour Immunology Group, Zentrum für Medizinische Forschung, University of Tübingen, Tübingen, Germany
- Health Sciences North Research Institute, Sudbury, ON, Canada
- John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, UK
| | - Parvez Iqbal Paracha
- Department of Human Nutrition, The Agriculture University Peshawar, Khyber Pakhtunkhwa, Pakistan
| |
Collapse
|
|
34
|
Zhu Y, Tong L, Nie K, Wiwatanaratanabutr I, Sun P, Li Q, Yu X, Wu P, Wu T, Yu C, Liu Q, Bian Z, Wang P, Cheng G. Host serum iron modulates dengue virus acquisition by mosquitoes. Nat Microbiol 2019; 4:2405-2415. [DOI: 10.1038/s41564-019-0555-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 08/06/2019] [Indexed: 12/14/2022]
|
|
35
|
Kato H, Igarashi K. To be red or white: lineage commitment and maintenance of the hematopoietic system by the "inner myeloid". Haematologica 2019; 104:1919-1927. [PMID: 31515352 PMCID: PMC6886412 DOI: 10.3324/haematol.2019.216861] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 05/10/2019] [Indexed: 12/21/2022] Open
Abstract
Differentiation of hematopoietic stem and progenitor cells is tightly regulated depending on environmental changes in order to maintain homeostasis. Transcription factors direct the development of hematopoietic cells, such as GATA-1 for erythropoiesis and PU.1 for myelopoiesis. However, recent findings obtained from single-cell analyses raise the question of whether these transcription factors are "initiators" or just "executors" of differentiation, leaving the initiation of hematopoietic stem and progenitor cell differentiation (i.e. lineage commitment) unclear. While a stochastic process is likely involved in commitment, it cannot fully explain the homeostasis of hematopoiesis nor "on-demand" hematopoiesis in response to environmental changes. Transcription factors BACH1 and BACH2 may regulate both commitment and on-demand hematopoiesis because they control erythroid-myeloid and lymphoid-myeloid differentiation by repressing the myeloid program, and their activities are repressed in response to infectious and inflammatory conditions. We summarize possible mechanisms of lineage commitment of hematopoietic stem and progenitor cells suggested by recent findings and discuss the erythroid and lymphoid commitment of hematopoietic stem and progenitor cells, focusing on the gene regulatory network composed of genes encoding key transcription factors. Surprising similarity exists between commitment to erythroid and lymphoid lineages, including repression of the myeloid program by BACH factors. The suggested gene regulatory network of BACH factors sheds light on the myeloid-based model of hematopoiesis. This model will help to understand the tuning of hematopoiesis in higher eukaryotes in the steady-state condition as well as in emergency conditions, the evolutional history of the system, aging and hematopoietic disorders.
Collapse
Affiliation(s)
- Hiroki Kato
- Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.,Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan.,Present address, Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Kazuhiko Igarashi
- Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan
| |
Collapse
|
|
36
|
Shisaka Y, Iwai Y, Yamada S, Uehara H, Tosha T, Sugimoto H, Shiro Y, Stanfield JK, Ogawa K, Watanabe Y, Shoji O. Hijacking the Heme Acquisition System of Pseudomonas aeruginosa for the Delivery of Phthalocyanine as an Antimicrobial. ACS Chem Biol 2019; 14:1637-1642. [PMID: 31287285 DOI: 10.1021/acschembio.9b00373] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
To survive in the iron-devoid environment of their host, pathogenic bacteria have devised multifarious cunning tactics such as evolving intricate heme transport systems to pirate extracellular heme. Yet, the potential of heme transport systems as antimicrobial targets has not been explored. Herein we developed a strategy to deliver antimicrobials by exploiting the extracellular heme acquisition system protein A (HasA) of Pseudomonas aeruginosa. We demonstrated that, analogous to heme uptake, HasA can specifically traffic an antimicrobial, gallium phthalocyanine (GaPc), into the intracellular space of P. aeruginosa via the interaction of HasA with its outer membrane receptor HasR. HasA enables water-insoluble GaPc to be mistakenly acquired by P. aeruginosa, permitting its sterilization (>99.99%) by irradiation with near-infrared (NIR) light, irrespective of antibiotic resistance. Our findings substantiate that bacterial heme uptake via protein-protein recognition is an attractive target for antimicrobials, enabling specific and effective sterilization.
Collapse
Affiliation(s)
- Yuma Shisaka
- Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan
| | - Yusuke Iwai
- Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan
| | - Shiho Yamada
- Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan
| | - Hiromu Uehara
- Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan
| | - Takehiko Tosha
- RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan
- Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan
| | - Hiroshi Sugimoto
- RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan
- Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan
| | - Yoshitsugu Shiro
- Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori, Ako, Hyogo 678-1297, Japan
| | - Joshua K. Stanfield
- Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan
| | - Kazuya Ogawa
- Department of Science for Advanced Materials, Faculty of Engineering, University of Yamanashi, 4-3-11 Takeda, Kofu, Yamanashi 400-8511, Japan
| | - Yoshihito Watanabe
- Research Center for Materials Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan
| | - Osami Shoji
- Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan
- Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan
| |
Collapse
|
|
37
|
Prevalence of anaemia among 6- to 59-month-old children in India: the latest picture through the NFHS-4. J Biosoc Sci 2019; 52:97-107. [PMID: 31104639 DOI: 10.1017/s0021932019000294] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
India is the highest contributor to child anaemia among developing countries. To see the latest picture of child anaemia in India, data for 6- to 59-month-old children were taken from the fourth round of the National Family Health Survey conducted in 2015-16 (NFHS-4). The study sample consisted of 1,37,347 children. The dependent variable was the anaemia status of the child. The objectives of the study were to assess (i) the distribution of anaemia prevalence by child age group, (ii) the prevalence of child anaemia by zone and state and (iii) the relation of child anaemia prevalence with social, demographic and economic variables, including maternal nutritional status and low birth weight. The study found that in India in 2015-16, 56% of 6- to 59-month-old children were anaemic - a decrease of only 13.5 percentage points since the NFHS-3 study conducted in 2005-06. It is well known that iron supplementation is necessary for child growth and brain development. This study suggests that, in addition, the socioeconomic conditions of households in India need to be improved to prevent child anaemia. Low birth weight and low maternal nutritional status are also responsible for the high prevalence of anaemia among children in India.
Collapse
|
|
38
|
Sarowska J, Futoma-Koloch B, Jama-Kmiecik A, Frej-Madrzak M, Ksiazczyk M, Bugla-Ploskonska G, Choroszy-Krol I. Virulence factors, prevalence and potential transmission of extraintestinal pathogenic Escherichia coli isolated from different sources: recent reports. Gut Pathog 2019; 11:10. [PMID: 30828388 PMCID: PMC6383261 DOI: 10.1186/s13099-019-0290-0] [Citation(s) in RCA: 392] [Impact Index Per Article: 65.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Accepted: 02/11/2019] [Indexed: 02/07/2023] Open
Abstract
Extraintestinal pathogenic E. coli (ExPEC) are facultative pathogens that are part of the normal human intestinal flora. The ExPEC group includes uropathogenic E. coli (UPEC), neonatal meningitis E. coli (NMEC), sepsis-associated E. coli (SEPEC), and avian pathogenic E. coli (APEC). Virulence factors (VF) related to the pathogenicity of ExPEC are numerous and have a wide range of activities, from those related to bacteria colonization to those related to virulence, including adhesins, toxins, iron acquisition factors, lipopolysaccharides, polysaccharide capsules, and invasins, which are usually encoded on pathogenicity islands (PAIs), plasmids and other mobile genetic elements. Mechanisms underlying the dynamics of ExPEC transmission and the selection of virulent clones are still poorly understood and require further research. The time shift between colonization of ExPEC and the development of infection remains problematic in the context of establishing the relation between consumption of contaminated food and the appearance of first disease symptoms. What appears to be most difficult is to prove that ExPEC strains cause disease symptoms and to examine the mechanism of transition from the asymptomatic colonization of the intestines to the spreading of the bacteria outside the digestive system. A significant problem for researchers who are trying to ascribe ExPEC transmission to food, people or the environment is to draw the distinction between colonization of ExPEC and infection. Food safety is an important challenge for public health both at the production stage and in the course of its processing and distribution. Examination of the genetic similarity of ExPEC strains will allow to determine their origin from different sources. Many levels of genotyping have been proposed in which the typing of strains, plasmids and genes is compared in order to obtain a more complete picture of this complex problem. The aim of our study was to characterize E. coli strains isolated from humans, animals and food for the presence of bacterial genes encoding virulence factors such as toxins, and iron acquisition systems (siderophores) in the context of an increasing spread of ExPEC infections.
Collapse
Affiliation(s)
- Jolanta Sarowska
- 1Department of Basic Sciences, Faculty of Health Sciences, Wroclaw Medical University, Chalubinskiego 4, 50-368 Wroclaw, Poland
| | - Bozena Futoma-Koloch
- 2Department of Microbiology, Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland
| | - Agnieszka Jama-Kmiecik
- 1Department of Basic Sciences, Faculty of Health Sciences, Wroclaw Medical University, Chalubinskiego 4, 50-368 Wroclaw, Poland
| | - Magdalena Frej-Madrzak
- 1Department of Basic Sciences, Faculty of Health Sciences, Wroclaw Medical University, Chalubinskiego 4, 50-368 Wroclaw, Poland
| | - Marta Ksiazczyk
- 2Department of Microbiology, Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland
| | - Gabriela Bugla-Ploskonska
- 2Department of Microbiology, Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland
| | - Irena Choroszy-Krol
- 1Department of Basic Sciences, Faculty of Health Sciences, Wroclaw Medical University, Chalubinskiego 4, 50-368 Wroclaw, Poland
| |
Collapse
|
|
39
|
Zhang X, Shen Y, Xu X, Zhang M, Bai Y, Miao Y, Fang Y, Zhang J, Wang R, Li J. Transcriptome analysis and histopathology of black carp (Mylopharyngodon piceus) spleen infected by Aeromonas hydrophila. FISH & SHELLFISH IMMUNOLOGY 2018; 83:330-340. [PMID: 30227254 DOI: 10.1016/j.fsi.2018.09.047] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2018] [Revised: 09/12/2018] [Accepted: 09/14/2018] [Indexed: 06/08/2023]
Abstract
Aeromonas hydrophila causes serious economic losses to the black carp (Mylopharyngodon piceus) industry. In this study, we analyzed the spleen of disease-resistant and susceptible black carp by RNA-seq. Overall, a total of 5243 terms were enriched in the gene ontology (GO) analysis, and 323 related pathways were found in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A total of 1935 differentially expressed genes were found and were primarily involved in cell adhesion, pathogen recognition, cellular immunity, cytokines, complement systems, and iron transport. Sixteen of the differently expressed genes involved in the immune response and the accuracy of the transcriptome data were further validated by quantitative real-time PCR (qRT-PCR). We observed Tissue sections of the spleen infected with A. hydrophila and the control group and found that the spleen of the infected group had necrosis.
Collapse
Affiliation(s)
- Xueshu Zhang
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China
| | - Yubang Shen
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China; Shanghai Engineering Research Center of Aquaculture, Shanghai Ocean University, Shanghai, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China
| | - Xiaoyan Xu
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China; Shanghai Engineering Research Center of Aquaculture, Shanghai Ocean University, Shanghai, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China
| | - Meng Zhang
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China
| | - Yulin Bai
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China
| | - Yiheng Miao
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China
| | - Yuan Fang
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China
| | - Jiahua Zhang
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China
| | - Rongquan Wang
- Key Laboratory of Conventional Freshwater Fish Breeding and Health Culture Technology Germplasm Resources, Suzhou Shenhang Eco-technology Development Limited Company, Suzhou, PR China
| | - Jiale Li
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai, China; Shanghai Engineering Research Center of Aquaculture, Shanghai Ocean University, Shanghai, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China.
| |
Collapse
|
|
40
|
Chao A, Sieminski PJ, Owens CP, Goulding CW. Iron Acquisition in Mycobacterium tuberculosis. Chem Rev 2018; 119:1193-1220. [PMID: 30474981 DOI: 10.1021/acs.chemrev.8b00285] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The highly contagious disease tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis (Mtb), which has been evolving drug resistance at an alarming rate. Like all human pathogens, Mtb requires iron for growth and virulence. Consequently, Mtb iron transport is an emerging drug target. However, the development of anti-TB drugs aimed at these metabolic pathways has been restricted by the dearth of information on Mtb iron acquisition. In this Review, we describe the multiple strategies utilized by Mtb to acquire ferric iron and heme iron. Mtb iron uptake is a complex process, requiring biosynthesis and subsequent export of Mtb siderophores, followed by ferric iron scavenging and ferric-siderophore import into Mtb. Additionally, Mtb possesses two possible heme uptake pathways and an Mtb-specific mechanism of heme degradation that yields iron and novel heme-degradation products. We conclude with perspectives for potential therapeutics that could directly target Mtb heme and iron uptake machineries. We also highlight how hijacking Mtb heme and iron acquisition pathways for drug import may facilitate drug transport through the notoriously impregnable Mtb cell wall.
Collapse
Affiliation(s)
| | | | - Cedric P Owens
- Schmid College of Science and Technology , Chapman University , Orange , California 92866 , United States
| | | |
Collapse
|
|
41
|
Na H, Kim Y, Kim D, Yoon H, Ryu S. Transcriptomic Analysis of Shiga Toxin-Producing Escherichia coli FORC_035 Reveals the Essential Role of Iron Acquisition for Survival in Canola Sprouts and Water Dropwort. Front Microbiol 2018; 9:2397. [PMID: 30349522 PMCID: PMC6186786 DOI: 10.3389/fmicb.2018.02397] [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: 05/17/2018] [Accepted: 09/19/2018] [Indexed: 12/03/2022] Open
Abstract
Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen that poses a serious threat to humans. Although EHEC is problematic mainly in food products containing meat, recent studies have revealed that many EHEC-associated foodborne outbreaks were attributable to spoiled produce such as sprouts and green leafy vegetables. To understand how EHEC adapts to the environment in fresh produce, we exposed the EHEC isolate FORC_035 to canola spouts (Brassica napus) and water dropwort (Oenanthe javanica) and profiled the transcriptome of this pathogen at 1 and 3 h after incubation with the plant materials. Transcriptome analysis revealed that the expression of genes associated with iron uptake were down-regulated during adaptation to plant tissues. A mutant strain lacking entB, presumably defective in enterobactin biosynthesis, had growth defects in co-culture with water dropwort, and the defective phenotype was complemented by the addition of ferric ion. Furthermore, gallium treatment to block iron uptake inhibited bacterial growth on water dropwort and also hampered biofilm formation. Taken together, these results indicate that iron uptake is essential for the fitness of EHEC in plants and that gallium can be used to prevent the growth of this pathogen in fresh produce.
Collapse
Affiliation(s)
- Hongjun Na
- Department of Food and Animal Biotechnology, Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea
| | - Yeonkyung Kim
- Department of Food and Animal Biotechnology, Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea
| | - Dajeong Kim
- Department of Food and Animal Biotechnology, Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea
| | - Hyunjin Yoon
- Department of Molecular Science and Technology, Department of Applied Chemistry and Biological Engineering, Ajou University, Suwon, South Korea
| | - Sangryeol Ryu
- Department of Food and Animal Biotechnology, Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.,Center for Food and Bioconvergence, Seoul National University, Seoul, South Korea
| |
Collapse
|
|
42
|
After the Fact(or): Posttranscriptional Gene Regulation in Enterohemorrhagic Escherichia coli O157:H7. J Bacteriol 2018; 200:JB.00228-18. [PMID: 29967119 DOI: 10.1128/jb.00228-18] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
To adapt to ever-changing environments, pathogens quickly alter gene expression. This can occur through transcriptional, posttranscriptional, or posttranslational regulation. Historically, transcriptional regulation has been thoroughly studied to understand pathogen niche adaptation, whereas posttranscriptional and posttranslational gene regulation has only relatively recently been appreciated to play a central role in bacterial pathogenesis. Posttranscriptional regulation may involve chaperones, nucleases, and/or noncoding small RNAs (sRNAs) and typically controls gene expression by altering the stability and/or translation of the target mRNA. In this review, we highlight the global importance of posttranscriptional regulation to enterohemorrhagic Escherichia coli (EHEC) gene expression and discuss specific mechanisms of how EHEC regulates expression of virulence factors critical to host colonization and disease progression. The low infectious dose of this intestinal pathogen suggests that EHEC is particularly well adapted to respond to the host environment.
Collapse
|
|
43
|
Sanders AJ, Taylor BW. Using ecological stoichiometry to understand and predict infectious diseases. OIKOS 2018. [DOI: 10.1111/oik.05418] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Affiliation(s)
- Andrew J. Sanders
- Dept of Applied Ecology; North Carolina State Univ.; Raleigh NC 27695 USA
- Rocky Mountain Biological Laboratory; Crested Butte CO 81224 USA
| | - Brad W. Taylor
- Dept of Applied Ecology; North Carolina State Univ.; Raleigh NC 27695 USA
- Rocky Mountain Biological Laboratory; Crested Butte CO 81224 USA
| |
Collapse
|
|
44
|
Peterson ND, Pukkila-Worley R. Caenorhabditis elegans in high-throughput screens for anti-infective compounds. Curr Opin Immunol 2018; 54:59-65. [PMID: 29935375 DOI: 10.1016/j.coi.2018.06.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 06/01/2018] [Accepted: 06/04/2018] [Indexed: 12/20/2022]
Abstract
New classes of antimicrobials that are effective therapies for infections with multi-drug resistant pathogens are urgently needed. The nematode Caenorhabditis elegans has been incorporated into small molecule screening platforms to identify anti-infective compounds that provide protection of a host during infection. The use of a live animal in these screening systems offers several advantages, including the ability to identify molecules that boost innate immune responses in a manner advantageous to host survival and compounds that disrupt bacterial virulence mechanisms. In addition, new classes of antimicrobials that target the pathogen have been uncovered, as well as interesting chemical probes that can be used to dissect new mechanisms of host-pathogen interactions.
Collapse
Affiliation(s)
- Nicholas D Peterson
- Program in Innate Immunity, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01655, United States
| | - Read Pukkila-Worley
- Program in Innate Immunity, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01655, United States.
| |
Collapse
|
|
45
|
Reddy VP, Chinta KC, Saini V, Glasgow JN, Hull TD, Traylor A, Rey-Stolle F, Soares MP, Madansein R, Rahman MA, Barbas C, Nargan K, Naidoo T, Ramdial PK, George JF, Agarwal A, Steyn AJC. Ferritin H Deficiency in Myeloid Compartments Dysregulates Host Energy Metabolism and Increases Susceptibility to Mycobacterium tuberculosis Infection. Front Immunol 2018; 9:860. [PMID: 29774023 PMCID: PMC5943674 DOI: 10.3389/fimmu.2018.00860] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Accepted: 04/06/2018] [Indexed: 12/20/2022] Open
Abstract
Iron is an essential factor for the growth and virulence of Mycobacterium tuberculosis (Mtb). However, little is known about the mechanisms by which the host controls iron availability during infection. Since ferritin heavy chain (FtH) is a major intracellular source of reserve iron in the host, we hypothesized that the lack of FtH would cause dysregulated iron homeostasis to exacerbate TB disease. Therefore, we used knockout mice lacking FtH in myeloid-derived cell populations to study Mtb disease progression. We found that FtH plays a critical role in protecting mice against Mtb, as evidenced by increased organ burden, extrapulmonary dissemination, and decreased survival in Fth-/- mice. Flow cytometry analysis showed that reduced levels of FtH contribute to an excessive inflammatory response to exacerbate disease. Extracellular flux analysis showed that FtH is essential for maintaining bioenergetic homeostasis through oxidative phosphorylation. In support of these findings, RNAseq and mass spectrometry analyses demonstrated an essential role for FtH in mitochondrial function and maintenance of central intermediary metabolism in vivo. Further, we show that FtH deficiency leads to iron dysregulation through the hepcidin-ferroportin axis during infection. To assess the clinical significance of our animal studies, we performed a clinicopathological analysis of iron distribution within human TB lung tissue and showed that Mtb severely disrupts iron homeostasis in distinct microanatomic locations of the human lung. We identified hemorrhage as a major source of metabolically inert iron deposition. Importantly, we observed increased iron levels in human TB lung tissue compared to healthy tissue. Overall, these findings advance our understanding of the link between iron-dependent energy metabolism and immunity and provide new insight into iron distribution within the spectrum of human pulmonary TB. These metabolic mechanisms could serve as the foundation for novel host-directed strategies.
Collapse
Affiliation(s)
- Vineel P. Reddy
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Krishna C. Chinta
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Vikram Saini
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Joel N. Glasgow
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Travis D. Hull
- Division of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Amie Traylor
- Nephrology Research and Training Center, University of Alabama at Birmingham and Birmingham VA Medical Center, Birmingham, AL, United States
| | - Fernanda Rey-Stolle
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain
| | | | - Rajhmun Madansein
- Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban, South Africa
| | | | - Coral Barbas
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain
| | - Kievershen Nargan
- Department of Anatomical Pathology, National Health Laboratory Service, University of KwaZulu-Natal, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
| | - Threnesan Naidoo
- Department of Anatomical Pathology, National Health Laboratory Service, University of KwaZulu-Natal, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
| | - Pratistadevi K. Ramdial
- Department of Anatomical Pathology, National Health Laboratory Service, University of KwaZulu-Natal, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
| | - James F. George
- Division of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Anupam Agarwal
- Nephrology Research and Training Center, University of Alabama at Birmingham and Birmingham VA Medical Center, Birmingham, AL, United States
| | - Adrie J. C. Steyn
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States
- Africa Health Research Institute (AHRI), Durban, South Africa
- UAB Centers for AIDS Research and Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, United States
| |
Collapse
|
|
46
|
Abstract
The host-adapted human pathogen Neisseria gonorrhoeae is the causative agent of gonorrhoea. Consistent with its proposed evolution from an ancestral commensal bacterium, N. gonorrhoeae has retained features that are common in commensals, but it has also developed unique features that are crucial to its pathogenesis. The continued worldwide incidence of gonorrhoeal infection, coupled with the rising resistance to antimicrobials and the difficulties in controlling the disease in developing countries, highlights the need to better understand the molecular basis of N. gonorrhoeae infection. This knowledge will facilitate disease prevention, surveillance and control, improve diagnostics and may help to facilitate the development of effective vaccines or new therapeutics. In this Review, we discuss sex-related symptomatic gonorrhoeal disease and provide an overview of the bacterial factors that are important for the different stages of pathogenesis, including transmission, colonization and immune evasion, and we discuss the problem of antibiotic resistance.
Collapse
Affiliation(s)
- Sarah Jane Quillin
- Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
| | - H Steven Seifert
- Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
| |
Collapse
|
|
47
|
Wang R, Dong L, He R, Wang Q, Chen Y, Qu L, Zhang YA. Comparative genomic analyses reveal the features for adaptation to nematodes in fungi. DNA Res 2018; 25:4791394. [PMID: 29315395 PMCID: PMC6014366 DOI: 10.1093/dnares/dsx053] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 12/06/2017] [Indexed: 12/20/2022] Open
Abstract
Nematophagous (NP) fungi are ecologically important components of the soil microbiome in natural ecosystems. Esteya vermicola (Ev) has been reported as a NP fungus with a poorly understood evolutionary history and mechanism of adaptation to parasitism. Furthermore, NP fungal genomic basis of lifestyle was still unclear. We sequenced and annotated the Ev genome (34.2 Mbp) and integrated genetic makeup and evolution of pathogenic genes to investigate NP fungi. The results revealed that NP fungi had some abundant pathogenic genes corresponding to their niche. A number of gene families involved in pathogenicity were expanded, and some pathogenic orthologous genes underwent positive selection. NP fungi with diverse morphological features exhibit similarities of evolutionary convergence in attacking nematodes, but their genetic makeup and microscopic mechanism are different. Endoparasitic NP fungi showed similarity in large number of transporters and secondary metabolite coding genes. Noteworthy, expanded families of transporters and endo-beta-glucanase implied great genetic potential of Ev in quickly perturbing nematode metabolism and parasitic behavior. These results facilitate our understanding of NP fungal genomic features for adaptation to nematodes and lay a solid theoretical foundation for further research and application.
Collapse
Affiliation(s)
- Ruizhen Wang
- The Key Laboratory of Forest Protection, State Forestry Administration of China, Research Institute of Forest Ecology, Environment and Protection, Chinese Academy of Forestry, Beijing 100091, China
- Institute of Botany, Beijing Botanical Garden, Beijing 100093, China
| | - Leiming Dong
- State Key Laboratory of Tree Genetics and Breeding, Research Institute of Forestry, Chinese Academy of Forestry, Beijing 100091, China
| | - Ran He
- The Key Laboratory of Forest Protection, State Forestry Administration of China, Research Institute of Forest Ecology, Environment and Protection, Chinese Academy of Forestry, Beijing 100091, China
- Institute of Botany, Beijing Botanical Garden, Beijing 100093, China
| | - Qinghua Wang
- The Key Laboratory of Forest Protection, State Forestry Administration of China, Research Institute of Forest Ecology, Environment and Protection, Chinese Academy of Forestry, Beijing 100091, China
| | - Yuequ Chen
- The Key Laboratory of Forest Protection, State Forestry Administration of China, Research Institute of Forest Ecology, Environment and Protection, Chinese Academy of Forestry, Beijing 100091, China
- Forestry Resources Protection Institute, Jilin Provincial Academy of Forestry Sciences, Changchun 130031, China
| | - Liangjian Qu
- The Key Laboratory of Forest Protection, State Forestry Administration of China, Research Institute of Forest Ecology, Environment and Protection, Chinese Academy of Forestry, Beijing 100091, China
| | - Yong-An Zhang
- The Key Laboratory of Forest Protection, State Forestry Administration of China, Research Institute of Forest Ecology, Environment and Protection, Chinese Academy of Forestry, Beijing 100091, China
| |
Collapse
|
|
48
|
Jiang J, Zhou Z, Dong Y, Zhao Z, Sun H, Wang B, Jiang B, Chen Z, Gao S. Comparative expression analysis of immune-related factors in the sea cucumber Apostichopus japonicus. FISH & SHELLFISH IMMUNOLOGY 2018; 72:342-347. [PMID: 29113862 DOI: 10.1016/j.fsi.2017.11.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Revised: 10/29/2017] [Accepted: 11/03/2017] [Indexed: 06/07/2023]
Abstract
In order to preliminarily explore the joint involvement of different immune-related factors during the same immune process in Apostichopus japonicus, the transcriptional expression of Cu/Zn superoxide dismutase (Cu/Zn-SOD), catalase (CAT), c-type lysozyme (c-LYZ), i-type lysozyme (i-LYZ), cathepsin D, melanotransferrin (MTF), Toll, c-type lectin (c-LCT) and complement 3 (C3) during the development from fertilized eggs to juveniles and after challenging the juveniles with Vibrio splendidus, Pseudoalteromonas nigrifaciens, Shewanella baltica and Bacillus cereus, respectively, was measured using the method of quantitative real-time PCR (qRT-PCR), and then the correlations among different immune-related factors were analyzed. The results showed that the selected immune-related factors were expressed at all of the determined developmental stages and significantly up-regulated at doliolaria stage, suggesting the selected factors are indispensable immune components and the immune system might be broadly activated at doliolaria stage in A. japonicus. After challenged with four pathogenic bacteria, Cu/Zn-SOD, CAT, i-LYZ, cathepsin D, MTF, Toll, C3 were all significantly down-regulated at 4 h, indicating that some components of A. japonicus immune system might be inhibited at the beginning of pathogenic bacteria invasion. The immune-responsive analysis also showed that the significant regulation in Toll after challenged with four tested bacteria, that in MTF after challenged with S. baltica and that in C3 after challenged with P. nigrifaciens were all minus, suggesting Toll, MTF and C3 are probably the primary targets of pathogenic bacteria attack. Furthermore, the correlation analysis indicated that, all of the selected immune-related factors except cathepsin D might be in the same immune regulatory network during A. japonicus development, while all of the selected immune-related factors except c-LYZ might be in the same responsive regulatory network after challenged with four pathogenic bacteria. Altogether, A. japonicus immune system exhibited high complexity in regulation during organism development and after bacterial challenges.
Collapse
Affiliation(s)
- Jingwei Jiang
- Liaoning Key Lab of Marine Fishery Molecular Biology, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Zunchun Zhou
- Liaoning Key Lab of Marine Fishery Molecular Biology, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China.
| | - Ying Dong
- Liaoning Key Lab of Marine Fishery Molecular Biology, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Zelong Zhao
- Liaoning Key Lab of Marine Fishery Molecular Biology, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Hongjuan Sun
- Liaoning Key Lab of Marine Fishery Molecular Biology, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Bai Wang
- Liaoning Key Lab of Marine Fishery Molecular Biology, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Bei Jiang
- Liaoning Key Lab of Marine Fishery Molecular Biology, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Zhong Chen
- Liaoning Key Lab of Marine Fishery Molecular Biology, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| | - Shan Gao
- Liaoning Key Lab of Marine Fishery Molecular Biology, Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning 116023, PR China
| |
Collapse
|
|
49
|
Kim JC, Wilcock P, Bedford MR. Iron status of piglets and impact of phytase superdosing on iron physiology: A review. Anim Feed Sci Technol 2018. [DOI: 10.1016/j.anifeedsci.2017.11.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
|
|
50
|
Heme-binding of bovine lactoferrin: the potential presence of a heme-binding capacity in an ancestral transferrin gene. Biometals 2017; 31:131-138. [DOI: 10.1007/s10534-017-0075-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Accepted: 12/19/2017] [Indexed: 10/18/2022]
|