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Fukuda K, Ito Y, Amagai M. Barrier Integrity and Immunity: Exploring the Cutaneous Front Line in Health and Disease. Annu Rev Immunol 2025; 43:219-252. [PMID: 40279307 DOI: 10.1146/annurev-immunol-082323-030832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/27/2025]
Abstract
Immune responses are influenced by not only immune cells but also the tissue microenvironment where these cells reside. Recent advancements in understanding the underlying molecular mechanisms and structures of the epidermal tight junctions (TJs) and stratum corneum (SC) have significantly enhanced our knowledge of skin barrier functions. TJs, located in the granular layer of the epidermis, are crucial boundary elements in the differentiation process, particularly in the transition from living cells to dead cells. The SC forms from dead keratinocytes via corneoptosis and features three distinct pH zones critical for barrier function and homeostasis. Additionally, the SC-skin microbiota interactions are crucial for modulating immune responses and protecting against pathogens. In this review, we explore how these components contribute both to healthy and disease states. By targeting the skin barrier in therapeutic strategies, we can enhance its integrity, modulate immune responses, and ultimately improve outcomes for patients with inflammatory skin conditions.
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Affiliation(s)
- Keitaro Fukuda
- Department of Dermatology, Keio University School of Medicine, Tokyo, Japan;
- Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan;
| | - Yoshihiro Ito
- Department of Dermatology, Keio University School of Medicine, Tokyo, Japan;
| | - Masayuki Amagai
- Department of Dermatology, Keio University School of Medicine, Tokyo, Japan;
- Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan;
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2
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Sela U, Heselpoth RD, Fischetti VA. Engineered Lysin-Derived Peptide as a Potent Antimicrobial for Acne Vulgaris. Antibiotics (Basel) 2025; 14:344. [PMID: 40298522 PMCID: PMC12024193 DOI: 10.3390/antibiotics14040344] [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: 02/10/2025] [Revised: 03/22/2025] [Accepted: 03/24/2025] [Indexed: 04/30/2025] Open
Abstract
Background/Objectives: Acne vulgaris is a skin disorder that affects millions worldwide, with Cutibacterium acnes playing a key role in its inflammation. Antibiotics reduce C. acnes and inflammation, but growing antibiotic resistance has limited their efficacy. Additionally, other common acne treatments with bactericidal activity, like benzoyl peroxide, cause irritation, dryness, and peeling. To fulfill the unmet need for alternative therapies, our strategy focused on identifying potent phage lysins and/or their derived cationic peptides. Methods: The C-terminal cationic antimicrobial peptide of the Prevotella intermedia phage lysin PlyPi01 was synthesized along with several sequence-engineered variants in an attempt to enhance their bactericidal efficacy. In vitro bacterial killing assays evaluated the potency of the lysin-derived peptide derivatives against C. acnes and Staphylococcus aureus, another skin bacterium associated with acne. Antibacterial activity was assessed both in conditions simulating the human skin and in combination with retinoids. Results: The variant peptide P156 was engineered by adding arginine residues at both the N- and C-terminal ends of the parental peptide PiP01. P156 was highly potent and eradicated all tested strains of C. acnes and S. aureus. P156 acted rapidly (>5-log kill in 10 min), further reducing the potential of resistance development. Additionally, P156 maintained its potency under conditions (e.g., temperature, pH, and salt concentration) observed on the skin surface and in hair follicles, as well as in combination with retinoid-all without being toxic to human cells. Conclusions: These collective findings position P156 as a promising topical drug for clinical applications to control acne vulgaris.
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Arantes AB, Rosa RT, de Oliveira NS, Bianchini LF, Rached RN, Johann ACBR, Weber SH, Murakami FS, Maluf DF, Rosa EAR. Facial disbiosis and UV filters. Arch Dermatol Res 2024; 316:739. [PMID: 39499337 DOI: 10.1007/s00403-024-03501-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 10/07/2024] [Accepted: 10/22/2024] [Indexed: 11/07/2024]
Abstract
Acne is a multifactorial inflammatory disease with a robust microbial component and numerous correlations with dysbiosis states. Furthermore, various factors are recognized as triggers for skin dysbiosis, including the use of certain cosmetics. Based on these arguments, we hypothesized that using photoprotective formulations could trigger dysbiosis and the occurrence of acne manifestations. To verify this assumption, six volunteers between 19 and 23 years of age, meeting all the inclusion criteria, received two applications a day of a non-commercial sunscreen formulation developed with the sun filters ethylhexyl methoxycinnamate, ethylhexyl salicylate, methyl anthranilate, and octocrylene dispersed in a base gel, with an estimated protection factor of 28.8. The pure base gel was used as a control. The samples were applied to an area delimited by a standard template (15 cm2) in an amount corresponding to 30 mg (2 mg cm2) for ten days. At two points in time, pre- and post-sample applications, the facial skin surface was swabbed to collect extracted DNA and processed to verify divergent degrees of 16 S RNA coding sequences. The data obtained allowed us to determine the abundance of different bacterial entities at the genus and species levels. The results showed that critical species of the acne process, such as Cutibacterium acnes and Staphylococcus epidermidis, seem to tolerate the evaluated formulation well and are not significantly affected by the formulation, suggesting no interference of its use concerning dysbiosis induction. These findings refute the idea that photoprotectors may cause skin dysbiosis in men.
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Affiliation(s)
- Angela Bonjorno Arantes
- School of Medicine and Life Sciences, Graduate Program on Dentistry, Pontifícia Universidade Católica do Paraná, 1155 Imaculada Conceição St. Zip, Curitiba, 80215-901, Brazil
| | - Rosimeire Takaki Rosa
- School of Medicine and Life Sciences. Xenobiotics Research Unit, Pontifícia Universidade Católica do Paraná, 1155 Imaculada Conceição St. Zip, Curitiba, 80215-901, Brazil
| | - Nicoly Subtil de Oliveira
- School of Medicine and Life Sciences, Graduate Program on Animal Science, Pontifícia Universidade Católica do Paraná, 1155 Imaculada Conceição St. Zip, Curitiba, 80215-901, Brazil
| | - Luiz Fernando Bianchini
- School of Medicine and Life Sciences. Xenobiotics Research Unit, Pontifícia Universidade Católica do Paraná, 1155 Imaculada Conceição St. Zip, Curitiba, 80215-901, Brazil
| | - Rodrigo Nunes Rached
- School of Medicine and Life Sciences, Graduate Program on Dentistry, Pontifícia Universidade Católica do Paraná, 1155 Imaculada Conceição St. Zip, Curitiba, 80215-901, Brazil
| | - Aline Cristina Batista Rodrigues Johann
- School of Medicine and Life Sciences, Graduate Program on Dentistry, Pontifícia Universidade Católica do Paraná, 1155 Imaculada Conceição St. Zip, Curitiba, 80215-901, Brazil
| | - Saulo Henrique Weber
- School of Medicine and Life Sciences, Graduate Program on Animal Science, Pontifícia Universidade Católica do Paraná, 1155 Imaculada Conceição St. Zip, Curitiba, 80215-901, Brazil
| | - Fábio Seigi Murakami
- Faculty of Pharmacy. Graduate Program on Pharmaceutical Sciences, Federal University of Paraná, 652 Prof. Lothario Meissner Av. Zip 80210-170, Curitiba, Brazil
| | - Daniela Florencio Maluf
- Faculty of Pharmacy. Graduate Program on Pharmaceutical Sciences, Federal University of Paraná, 652 Prof. Lothario Meissner Av. Zip 80210-170, Curitiba, Brazil
| | - Edvaldo Antonio Ribeiro Rosa
- School of Medicine and Life Sciences, Graduate Program on Dentistry, Pontifícia Universidade Católica do Paraná, 1155 Imaculada Conceição St. Zip, Curitiba, 80215-901, Brazil.
- School of Medicine and Life Sciences. Xenobiotics Research Unit, Pontifícia Universidade Católica do Paraná, 1155 Imaculada Conceição St. Zip, Curitiba, 80215-901, Brazil.
- School of Medicine and Life Sciences, Graduate Program on Animal Science, Pontifícia Universidade Católica do Paraná, 1155 Imaculada Conceição St. Zip, Curitiba, 80215-901, Brazil.
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Bérard JB, Ouk TS, Sol V, Lefoulon L, Landolt C, Grenier K, Saad N, Robert E, Sibat M, Schreiber N, Guenin S, Picot L. Phototoxicity of the Ethanolic Extract of Skeletonema marinoi for the Dermocosmetic Improvement of Acne. Mar Drugs 2024; 22:343. [PMID: 39195459 DOI: 10.3390/md22080343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 07/25/2024] [Accepted: 07/26/2024] [Indexed: 08/29/2024] Open
Abstract
Acne is one of the most common dermatological conditions, peaking during adolescence and early adulthood, affecting about 85% of individuals aged 12-24. Although often associated with teenage years, acne can occur at any age, impacting over 25% of women and 12% of men in their forties. Treatment strategies vary depending on the severity, including the use of topical gels or creams containing benzoyl peroxide and retinoids, antibiotics, and systemic or topical isotretinoin. However, these treatments can cause irritation, allergies, and other toxic side effects. Currently, there is no natural-based alternative for antibacterial photodynamic therapy targeting acne using marine drugs or extracts. Through a bioguided screening approach, we identified the ethanol extract of Skeletonema marinoi as highly phototoxic against three bacterial species associated with acne-Cutibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis. This extract exhibited phototoxicity in planktonic bacteria under white and red light, disrupted bacterial biofilms, reduced sebum production but also showed phototoxicity in keratinocytes, highlighting the importance of the specific targeting of treatment areas. Further investigations, including fractionation and high-resolution structural analysis, linked the observed phototoxicity to a high concentration of pheophorbide a in the extract. Given its notable in vitro efficacy, this extract holds promising potential for clinical evaluation to manage mild acne. This discovery paves the way for further exploration of Skeletonema pigment extracts, extending their potential applications beyond acne phototherapy to include dermocosmetics, veterinary medicine, and other phototherapy uses.
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Affiliation(s)
- Jean-Baptiste Bérard
- French Research Institute for Exploitation of the Sea (IFREMER), PHYTOX, 44000 Nantes, France
| | - Tan-Sothea Ouk
- Laboratoire des Agroressources, Biomolécules et Chimie pour l'Innovation en Santé (LABCiS), University of Limoges, UR 22722, 87000 Limoges, France
| | - Vincent Sol
- Laboratoire des Agroressources, Biomolécules et Chimie pour l'Innovation en Santé (LABCiS), University of Limoges, UR 22722, 87000 Limoges, France
| | - Louise Lefoulon
- French Research Institute for Exploitation of the Sea (IFREMER), PHYTOX, 44000 Nantes, France
| | - Cornelia Landolt
- Laboratoire des Agroressources, Biomolécules et Chimie pour l'Innovation en Santé (LABCiS), University of Limoges, UR 22722, 87000 Limoges, France
| | - Karine Grenier
- Laboratoire des Agroressources, Biomolécules et Chimie pour l'Innovation en Santé (LABCiS), University of Limoges, UR 22722, 87000 Limoges, France
| | - Naima Saad
- Laboratoire des Agroressources, Biomolécules et Chimie pour l'Innovation en Santé (LABCiS), University of Limoges, UR 22722, 87000 Limoges, France
| | - Elise Robert
- French Research Institute for Exploitation of the Sea (IFREMER), PHYTOX, 44000 Nantes, France
| | - Manoëlla Sibat
- French Research Institute for Exploitation of the Sea (IFREMER), PHYTOX, 44000 Nantes, France
| | - Nathalie Schreiber
- French Research Institute for Exploitation of the Sea (IFREMER), PHYTOX, 44000 Nantes, France
| | | | - Laurent Picot
- UMR CNRS 7266 LIENSs, La Rochelle Université, 17042 La Rochelle, France
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Nong Y, Walsh DM, Maloh J, Dadlani M, Sivamani R. Whole-Genome Shotgun Metagenomic Sequencing Reveals Shifts in the Skin Microbiome and Bacteriophages of Psoriasis: An Extended Analysis of Published Data. JOURNAL OF PSORIASIS AND PSORIATIC ARTHRITIS 2024; 9:98-107. [PMID: 39301212 PMCID: PMC11361494 DOI: 10.1177/24755303241242357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/22/2024]
Abstract
Background Psoriasis is an immune-mediated cutaneous disease that may have shifts in the skin microbiome. Prior research on the skin microbiome in psoriasis has been limited to rRNA based approaches that lack resolution of taxonomic and functional level assessment. Objective To further illuminate strain and sub-strain level analysis of psoriatic lesions using the CosmosID-HUB Microbiome pipeline. Methods A previous study completed by Tett et al recruited patients with psoriasis who had skin microbiome samples taken from psoriatic plaques on the ear and the elbow as well as sites on the skin unaffected by psoriasis. They performed whole genome shotgun sequencing and made their dataset publicly available. We analyzed the dataset using the CosmosID-HUB Microbiome pipeline to evaluate the strain and sub-strain taxonomic analysis as well as functional gene profiling. Results When analyzed with the CosmosID pipeline, both ear and elbow sites in affected areas had decreased alpha diversity compared to unaffected areas. There was an increased relative abundance of Staphylococcus and Corynebacteria at affected sites. We identified distinguishing species and strains of the yeast Malassezia, including M. restricta. that were significantly enriched in healthy elbow samples. Vitamin B12 production genes were not present in psoriatic skin whereas it was present in healthy samples, supporting the notion of relative vitamin B12 deficiency in psoriatic plaques. Phage analysis revealed a greater diversity of Staphylococcus-related phages in unaffected elbow samples. Conclusion A greater diversity of microbial strains and their functional roles identified in this study may help to tailor treatment for psoriasis.
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Affiliation(s)
- Yvonne Nong
- SUNY Downstate Medical Center, Brooklyn, NY, USA
- Integrative Skin Science and Research, Sacramento, CA, USA
- Pacific Skin Institute, Sacramento, CA, USA
- Department of Dermatology, University of California-Davis, Sacramento, CA, USA
| | | | - Jessica Maloh
- Integrative Skin Science and Research, Sacramento, CA, USA
| | | | - Raja Sivamani
- Integrative Skin Science and Research, Sacramento, CA, USA
- Pacific Skin Institute, Sacramento, CA, USA
- Department of Dermatology, University of California-Davis, Sacramento, CA, USA
- College of Medicine, California Northstate University, Elk Grove, CA, USA
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Zhao H, Shang L, Zhang Y, Liang Z, Wang N, Zhang Q, Gao C, Luo J. IL-17A inhibitors alleviate Psoriasis with concomitant restoration of intestinal/skin microbiota homeostasis and altered microbiota function. Front Immunol 2024; 15:1344963. [PMID: 38482003 PMCID: PMC10933079 DOI: 10.3389/fimmu.2024.1344963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 02/12/2024] [Indexed: 04/12/2024] Open
Abstract
Background Disturbed gut microbiota and associated metabolic dysfunction exist in Psoriasis. Despite the growing use of interleukin-17 inhibitor (anti-IL17) therapy, the effect of anti-IL17 on gut/skin microbiota function is not fully understood in patients with Psoriasis. Objective Therefore, we explored whether Psoriasis is associated with alterations in selected gut/skin microbiota in a study cohort, and a longitudinal cohort study to reveal the effects of IL-17A inhibitor treatment on gut microbiota in Psoriasis. Methods In a case-control study, 14 patients with Psoriasis and 10 age, sex and body mass index-matched Healthy Controls were recruited. Longitudinal mapping of the gut microbiome was performed using 16S rRNA gene sequencing. Mouse models were used to further study and validate the interrelationship between the skin microbiome and the gut microbiome in Psoriasis. PICRUST2 was applied to predict the function of the bacterial community. Results In Psoriasis patients, gut microbiota dysbiosis was present with increased heterogeneity: decreased Bacteroidota and increased Firmicutes as well as Actinobacteriota predominating in Psoriasis. Escherichia-Shigella enrichment was associated with reduction in serum levels of total bile acid and markers in Apoptotic pathways. After IL-17A inhibitor treatment in Psoriasis patients, longitudinal studies observed a trend toward a normal distribution of the gut microbiome and modulation of apoptosis-related metabolic pathways. Results from a mouse model showed dysregulation of the skin microbiota in Psoriasis characterized by Staphylococcus colonization. Conclusion The psoriatic gut/skin microbiota exhibits loss of community stability and pathogen enrichment. IL-17A inhibitors restore microbiota homeostasis and metabolic pathways, reduce pro-inflammatory cytokine expression, and alleviate symptoms in patients with Psoriasis.
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Affiliation(s)
- Huixia Zhao
- Department of Dermatology, Heji Hospital of Changzhi Medical College, Changzhi, China
| | - Lili Shang
- Department of Rheumatology, The Second Clinical Medical College of Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory for immunomicroecology, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Yuting Zhang
- Department of Dermatology, Heji Hospital of Changzhi Medical College, Changzhi, China
| | - Zhaojun Liang
- Shanxi Key Laboratory for immunomicroecology, The Second Hospital of Shanxi Medical University, Taiyuan, China
- Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Nan Wang
- Shanxi Key Laboratory for immunomicroecology, The Second Hospital of Shanxi Medical University, Taiyuan, China
- Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Qian Zhang
- Department of Dermatology, Heji Hospital of Changzhi Medical College, Changzhi, China
| | - Chong Gao
- Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
| | - Jing Luo
- Shanxi Key Laboratory for immunomicroecology, The Second Hospital of Shanxi Medical University, Taiyuan, China
- Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, China
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Gehrke AKE, Giai C, Gómez MI. Staphylococcus aureus Adaptation to the Skin in Health and Persistent/Recurrent Infections. Antibiotics (Basel) 2023; 12:1520. [PMID: 37887220 PMCID: PMC10604630 DOI: 10.3390/antibiotics12101520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/03/2023] [Accepted: 10/04/2023] [Indexed: 10/28/2023] Open
Abstract
Staphylococcus aureus is a microorganism with an incredible capability to adapt to different niches within the human body. Approximately between 20 and 30% of the population is permanently but asymptomatically colonized with S. aureus in the nose, and another 30% may carry S. aureus intermittently. It has been established that nasal colonization is a risk factor for infection in other body sites, including mild to severe skin and soft tissue infections. The skin has distinct features that make it a hostile niche for many bacteria, therefore acting as a strong barrier against invading microorganisms. Healthy skin is desiccated; it has a low pH at the surface; the upper layer is constantly shed to remove attached bacteria; and several host antimicrobial peptides are produced. However, S. aureus is able to overcome these defenses and colonize this microenvironment. Moreover, this bacterium can very efficiently adapt to the stressors present in the skin under pathological conditions, as it occurs in patients with atopic dermatitis or suffering chronic wounds associated with diabetes. The focus of this manuscript is to revise the current knowledge concerning how S. aureus adapts to such diverse skin conditions causing persistent and recurrent infections.
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Affiliation(s)
- Ana-Katharina E. Gehrke
- Centro de Estudios Biomédicos, Básicos, Aplicados y Desarrollo (CEBBAD), Departamento de Investigaciones Biomédicas y Biotecnológicas, Universidad Maimónides, Buenos Aires C1405BCK, Argentina;
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires C1425FQB, Argentina
| | - Constanza Giai
- Instituto de Histología y Embriología de Mendoza, Universidad Nacional de Cuyo—(UNCuyo) CONICET, Mendoza M5502JMA, Argentina;
- Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza M5502JMA, Argentina
- Facultad de Farmacia y Bioquímica, Universidad Juan Agustín Maza, Mendoza C1006ACC, Argentina
| | - Marisa I. Gómez
- Centro de Estudios Biomédicos, Básicos, Aplicados y Desarrollo (CEBBAD), Departamento de Investigaciones Biomédicas y Biotecnológicas, Universidad Maimónides, Buenos Aires C1405BCK, Argentina;
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires C1425FQB, Argentina
- Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121A6B, Argentina
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Boncompain CA, Suárez CA, Squeff M, Belluzo V, Piccirilli G, Molteni A, Fernández Bussy RA, Morbidoni HR. Phenotypic and molecular characterization of Staphylococcus aureus isolates conducted in nares of psoriatic patients attending a public hospital in Argentina. Rev Argent Microbiol 2023; 55:3-11. [PMID: 35760653 DOI: 10.1016/j.ram.2022.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Revised: 12/14/2021] [Accepted: 02/14/2022] [Indexed: 11/28/2022] Open
Abstract
Although Staphylococcus aureus increases its relative abundance in psoriasis when compared with the microbiome of healthy subjects, it is not the most important microorganism underlying this disease. However, there is scant data on the role and molecular features of S. aureus strains in psoriasis; therefore, the aim of this study was to evaluate nasal carriage of this microorganism, its phenotypic and molecular characteristics as well as the impact of host factors on its carriage in psoriatic patients. The presence of S. aureus was analyzed in nasal swabs from 46 healthy volunteers and 50 psoriatic patients by conventional microbiology techniques. Nasal carriage of S. aureus was higher in psoriatic patients than in the control group (37.24% vs 22.98%, respectively), being associated to sex (male), age (adults) and severity of the disease (more frequent in moderate and severe cases). Determination of antibiotic resistance detected 12% of β-lactam resistant isolates, with variable accompanying resistance to macrolides, aminoglycosides and fluoroquinolones. No resistance to rifampicin, vancomycin, mupirocin or trimethoprim/sulfamethoxazole was found. A preliminary molecular characterization of the isolates was performed by PCR amplification of virulence genes. Molecular characterization of the strains did not reveal a predominant strain in psoriatic patients. Although we established host factors related to increased carriage of S. aureus in psoriatic patients, we could not establish the predominance of one type of strain. Genomic and transcriptomic analysis of the isolated strains would be necessary to address this point.
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Affiliation(s)
- Carina A Boncompain
- Laboratorio de Microbiología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina
| | - Cristian A Suárez
- Laboratorio de Microbiología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina; Consejo Nacional de Investigaciones Científicas y Tecnológicas, CONICET, Argentina
| | - Mario Squeff
- Cátedra de Dermatología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina
| | - Valeria Belluzo
- Cátedra de Dermatología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina
| | - Gustavo Piccirilli
- Cátedra de Dermatología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina
| | - Ana Molteni
- Cátedra de Dermatología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina
| | - Ramón A Fernández Bussy
- Cátedra de Dermatología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina.
| | - Héctor R Morbidoni
- Laboratorio de Microbiología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario, Argentina; Consejo de Investigaciones, Universidad Nacional de Rosario, Maipú 1065, Rosario, Argentina.
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Silva LADA, Ramos LP, Silva TA, Lapena SABDE, Santos CER, Hasna AA, Bressane A, Oliveira LDDE. Effect of combining Zingiber officinale and Juglans regia extracts on Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis: antibiofilm action and low toxicity. AN ACAD BRAS CIENC 2022; 94:e20201133. [PMID: 36449895 DOI: 10.1590/0001-3765202220201133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 12/11/2020] [Indexed: 11/27/2022] Open
Abstract
Objective was evaluated the therapeutic effect of Juglans regia (J) and Zingiber officinale (Z) extracts, alone or associated (Z75% + J25%, Z50% + J50% and Z25% + J75%) applied on planktonic cultures and biofilms of Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus, as well as analyzing the cytotoxic effects of plant extracts on mouse macrophages (Raw 264-7). Broth microdilution assay was performed (M7-A6 - CLSI). Anti-biofilm activities and cytotoxicity on Raw 264-7 were studied using MTT assay and scanning electron microscopy. ANOVA with post-hoc Tukey HSD applied for parametric data and Kruskal-Wallis with Conover-Iman test, for non-parametric (p<0.05). On P. acnes biofilm, Z50% + J50% reduced 46.9% in 5 min and Z25% + J75% reduced 74.1% in 24hs. On S. aureus, Z75% + J25% reduced 23.1% in 5 min Z25% +J75% reduced 79.4% in 24hs. On S. epidermidis, Z75% + J25% reduced 74.6% in 5 min and 82.05% in 24 h. The treatments on macrophages for 24 h promoted a maximum reduction by 14,5% for groups of extracts associations. On multispecies biofilm, Z75%+J25% reduced 84.3% in 24 h. In conclusion association of glycolic extracts provided therapeutic effect, demonstrated antimicrobial activity and low cytotoxicity.
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Affiliation(s)
- Leonardo A DA Silva
- Universidade Estadual Paulista/ UNESP, Instituto de Ciencia e Tecnologia, Departamento de Biociências e Diagnóstico Bucal, Av. Eng. Francisco José Longo, 777, São Dimas, 12245-000 São José dos Campos, SP, Brazil
- Instituto Taubaté de Ensino Superior/ITES, Departamento de Ciências da Saúde, Av. Dom Pedro I, 3575, Jardim Eulália, 12090-000 Taubaté, SP, Brazil
| | - Lucas P Ramos
- Universidade Estadual Paulista/ UNESP, Instituto de Ciencia e Tecnologia, Departamento de Biociências e Diagnóstico Bucal, Av. Eng. Francisco José Longo, 777, São Dimas, 12245-000 São José dos Campos, SP, Brazil
- Instituto Taubaté de Ensino Superior/ITES, Departamento de Ciências da Saúde, Av. Dom Pedro I, 3575, Jardim Eulália, 12090-000 Taubaté, SP, Brazil
| | - Tatiane A Silva
- Universidade Estadual Paulista/ UNESP, Instituto de Ciencia e Tecnologia, Departamento de Biociências e Diagnóstico Bucal, Av. Eng. Francisco José Longo, 777, São Dimas, 12245-000 São José dos Campos, SP, Brazil
- Instituto Taubaté de Ensino Superior/ITES, Departamento de Ciências da Saúde, Av. Dom Pedro I, 3575, Jardim Eulália, 12090-000 Taubaté, SP, Brazil
| | - Simone A B DE Lapena
- Universidade Estadual Paulista/ UNESP, Instituto de Ciencia e Tecnologia, Departamento de Biociências e Diagnóstico Bucal, Av. Eng. Francisco José Longo, 777, São Dimas, 12245-000 São José dos Campos, SP, Brazil
- Instituto Taubaté de Ensino Superior/ITES, Departamento de Ciências da Saúde, Av. Dom Pedro I, 3575, Jardim Eulália, 12090-000 Taubaté, SP, Brazil
| | - Carlos Eduardo R Santos
- Universidade Estadual Paulista/ UNESP, Instituto de Ciencia e Tecnologia, Departamento de Biociências e Diagnóstico Bucal, Av. Eng. Francisco José Longo, 777, São Dimas, 12245-000 São José dos Campos, SP, Brazil
- Instituto Policlin de Ensino e Pesquisas/IPEP, Av. Nove de Julho, 430, Vila Ady'Anna, 12243-001 São José dos Campos, SP, Brazil
| | - Amjad A Hasna
- Universidade Estadual Paulista/UNESP, Instituto de Ciencia e Tecnologia, Departamento de Odontologia Restauradora, Divisão de Endodontia, Av. Eng. Francisco José Longo, 777, São Dimas, 12245-000 São José dos Campos, SP, Brazil
| | - Adriano Bressane
- Universidade Estadual Paulista/ UNESP, Instituto de Ciencia e Tecnologia, Departamento de Biociências e Diagnóstico Bucal, Av. Eng. Francisco José Longo, 777, São Dimas, 12245-000 São José dos Campos, SP, Brazil
| | - Luciane D DE Oliveira
- Universidade Estadual Paulista/ UNESP, Instituto de Ciencia e Tecnologia, Departamento de Biociências e Diagnóstico Bucal, Av. Eng. Francisco José Longo, 777, São Dimas, 12245-000 São José dos Campos, SP, Brazil
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10
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Ito Y, Amagai M. Controlling skin microbiome as a new bacteriotherapy for inflammatory skin diseases. Inflamm Regen 2022; 42:26. [PMID: 36045395 PMCID: PMC9434865 DOI: 10.1186/s41232-022-00212-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 05/10/2022] [Indexed: 11/12/2022] Open
Abstract
The skin serves as the interface between the human body and the environment and interacts with the microbial community. The skin microbiota consists of microorganisms, such as bacteria, fungi, mites, and viruses, and they fluctuate depending on the microenvironment defined by anatomical location and physiological function. The balance of interactions between the host and microbiota plays a pivotal role in the orchestration of skin homeostasis; however, the disturbance of the balance due to an alteration in the microbial communities, namely, dysbiosis, leads to various skin disorders. Recent developments in sequencing technology have provided new insights into the structure and function of skin microbial communities. Based on high-throughput sequencing analysis, a growing body of evidence indicates that a new treatment using live bacteria, termed bacteriotherapy, is a feasible therapeutic option for cutaneous diseases caused by dysbiosis. In particular, the administration of specific bacterial strains has been investigated as an exclusionary treatment strategy against pathogens associated with chronic skin disorders, whereas the safety, efficacy, and sustainability of this therapeutic approach using isolated live bacteria need to be further explored. In this review, we summarize our current understanding of the skin microbiota, as well as therapeutic strategies using characterized strains of live bacteria for skin inflammatory diseases. The ecosystem formed by interactions between the host and skin microbial consortium is still largely unexplored; however, advances in our understanding of the function of the skin microbiota at the strain level will lead to the development of new therapeutic methods.
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Affiliation(s)
- Yoshihiro Ito
- Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
| | - Masayuki Amagai
- Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.,RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan
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11
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Grando K, Nicastro LK, Tursi SA, De Anda J, Lee EY, Wong GCL, Tükel Ç. Phenol-Soluble Modulins From Staphylococcus aureus Biofilms Form Complexes With DNA to Drive Autoimmunity. Front Cell Infect Microbiol 2022; 12:884065. [PMID: 35646719 PMCID: PMC9131096 DOI: 10.3389/fcimb.2022.884065] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 04/04/2022] [Indexed: 12/15/2022] Open
Abstract
The bacterial amyloid curli, produced by Enterobacteriales including Salmonella species and Escherichia coli, is implicated in the pathogenesis of several complex autoimmune diseases. Curli binds to extracellular DNA, and these complexes drive autoimmunity via production of anti-double-stranded DNA autoantibodies. Here, we investigated immune activation by phenol-soluble modulins (PSMs), the amyloid proteins expressed by Staphylococcus species. We confirmed the amyloid nature of PSMs expressed by S. aureus using a novel specific amyloid stain, (E,E)-1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy) styrylbenzene (FSB). Direct interaction of one of the S. aureus PSMs, PSMα3, with oligonucleotides promotes fibrillization of PSM amyloids and complex formation with bacterial DNA. Finally, utilizing a mouse model with an implanted mesh-associated S. aureus biofilm, we demonstrated that exposure to S. aureus biofilms for six weeks caused anti-double-stranded DNA autoantibody production in a PSM-dependent manner. Taken together, these results highlight how the presence of PSM-DNA complexes in S. aureus biofilms can induce autoimmune responses, and suggest an explanation for how bacterial infections trigger autoimmunity.
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Affiliation(s)
- Kaitlyn Grando
- Center for Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Lauren K. Nicastro
- Center for Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Sarah A. Tursi
- Center for Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
| | - Jaime De Anda
- Department of Bioengineering, Department of Chemistry and Biochemistry, California Nano Systems Institute, University of California, Los Angeles, Los Angeles, CA, United States
| | - Ernest Y. Lee
- Department of Bioengineering, Department of Chemistry and Biochemistry, California Nano Systems Institute, University of California, Los Angeles, Los Angeles, CA, United States
| | - Gerard C. L. Wong
- Department of Bioengineering, Department of Chemistry and Biochemistry, California Nano Systems Institute, University of California, Los Angeles, Los Angeles, CA, United States
| | - Çağla Tükel
- Center for Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
- *Correspondence: Çağla Tükel,
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12
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Cesaro A, Torres MDT, Gaglione R, Dell'Olmo E, Di Girolamo R, Bosso A, Pizzo E, Haagsman HP, Veldhuizen EJA, de la Fuente-Nunez C, Arciello A. Synthetic Antibiotic Derived from Sequences Encrypted in a Protein from Human Plasma. ACS NANO 2022; 16:1880-1895. [PMID: 35112568 DOI: 10.1021/acsnano.1c04496] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Encrypted peptides have been recently found in the human proteome and represent a potential class of antibiotics. Here we report three peptides derived from the human apolipoprotein B (residues 887-922) that exhibited potent antimicrobial activity against drug-resistant Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococci both in vitro and in an animal model. The peptides had excellent cytotoxicity profiles, targeted bacteria by depolarizing and permeabilizing their cytoplasmic membrane, inhibited biofilms, and displayed anti-inflammatory properties. Importantly, the peptides, when used in combination, potentiated the activity of conventional antibiotics against bacteria and did not select for bacterial resistance. To ensure translatability of these molecules, a protease resistant retro-inverso variant of the lead encrypted peptide was synthesized and demonstrated anti-infective activity in a preclinical mouse model. Our results provide a link between human plasma and innate immunity and point to the blood as a source of much-needed antimicrobials.
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Affiliation(s)
- Angela Cesaro
- Department of Chemical Sciences, University of Naples Federico II, Naples I-80126, Italy
- Department of Biomolecular Health Sciences, Division of Infectious Diseases and Immunology, Section Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, The Netherlands
- Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
- Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
- Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Marcelo D T Torres
- Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
- Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
- Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Rosa Gaglione
- Department of Chemical Sciences, University of Naples Federico II, Naples I-80126, Italy
- Istituto Nazionale di Biostrutture e Biosistemi (INBB), Rome 00136, Italy
| | - Eliana Dell'Olmo
- Department of Chemical Sciences, University of Naples Federico II, Naples I-80126, Italy
| | - Rocco Di Girolamo
- Department of Chemical Sciences, University of Naples Federico II, Naples I-80126, Italy
| | - Andrea Bosso
- Department of Biology, University of Naples Federico II, Naples I-80126, Italy
| | - Elio Pizzo
- Department of Biology, University of Naples Federico II, Naples I-80126, Italy
| | - Henk P Haagsman
- Department of Biomolecular Health Sciences, Division of Infectious Diseases and Immunology, Section Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, The Netherlands
| | - Edwin J A Veldhuizen
- Department of Biomolecular Health Sciences, Division of Infectious Diseases and Immunology, Section Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, The Netherlands
| | - Cesar de la Fuente-Nunez
- Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
- Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
- Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Angela Arciello
- Department of Chemical Sciences, University of Naples Federico II, Naples I-80126, Italy
- Istituto Nazionale di Biostrutture e Biosistemi (INBB), Rome 00136, Italy
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13
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Tuft S, Somerville TF, Li JPO, Neal T, De S, Horsburgh MJ, Fothergill JL, Foulkes D, Kaye S. Bacterial keratitis: identifying the areas of clinical uncertainty. Prog Retin Eye Res 2021; 89:101031. [PMID: 34915112 DOI: 10.1016/j.preteyeres.2021.101031] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 11/24/2021] [Accepted: 11/29/2021] [Indexed: 12/12/2022]
Abstract
Bacterial keratitis is a common corneal infection that is treated with topical antimicrobials. By the time of presentation there may already be severe visual loss from corneal ulceration and opacity, which may persist despite treatment. There are significant differences in the associated risk factors and the bacterial isolates between high income and low- or middle-income countries, so that general management guidelines may not be appropriate. Although the diagnosis of bacterial keratitis may seem intuitive there are multiple uncertainties about the criteria that are used, which impacts the interpretation of investigations and recruitment to clinical studies. Importantly, the concept that bacterial keratitis can only be confirmed by culture ignores the approximately 50% of cases clinically consistent with bacterial keratitis in which investigations are negative. The aetiology of these culture-negative cases is unknown. Currently, the estimation of bacterial susceptibility to antimicrobials is based on data from systemic administration and achievable serum or tissue concentrations, rather than relevant corneal concentrations and biological activity in the cornea. The provision to the clinician of minimum inhibitory concentrations of the antimicrobials for the isolated bacteria would be an important step forward. An increase in the prevalence of antimicrobial resistance is a concern, but the effect this has on disease outcomes is yet unclear. Virulence factors are not routinely assessed although they may affect the pathogenicity of bacteria within species and affect outcomes. New technologies have been developed to detect and kill bacteria, and their application to bacterial keratitis is discussed. In this review we present the multiple areas of clinical uncertainty that hamper research and the clinical management of bacterial keratitis, and we address some of the assumptions and dogma that have become established in the literature.
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Affiliation(s)
- Stephen Tuft
- Moorfields Eye Hospital NHS Foundation Trust, 162 City Road, London, EC1V 2PD, UK.
| | - Tobi F Somerville
- Department of Eye and Vision Sciences, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.
| | - Ji-Peng Olivia Li
- Moorfields Eye Hospital NHS Foundation Trust, 162 City Road, London, EC1V 2PD, UK.
| | - Timothy Neal
- Department of Clinical Microbiology, Liverpool Clinical Laboratories, Liverpool University Hospital NHS Foundation Trust, Prescot Street, Liverpool, L7 8XP, UK.
| | - Surjo De
- Department of Clinical Microbiology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London, NW1 2PG, UK.
| | - Malcolm J Horsburgh
- Department of Infection and Microbiomes, University of Liverpool, Crown Street, Liverpool, L69 7BX, UK.
| | - Joanne L Fothergill
- Department of Eye and Vision Sciences, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.
| | - Daniel Foulkes
- Department of Eye and Vision Sciences, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.
| | - Stephen Kaye
- Department of Eye and Vision Sciences, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.
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14
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Sembiring KS, Jusuf NK. Cell Phone Acne: New Acne Clinical Features in the Coronavirus Disease-19 Era. Open Access Maced J Med Sci 2021. [DOI: 10.3889/oamjms.2021.6872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Technological developments in telecommunications, especially cell phone, enable us to keep communicate without meeting each other. Especially during the latest coronavirus outbreak, when people need to keep up social distance. Meanwhile, electronic devices such as smartphone, tablets, laptops, and light-emitting diode screens are the sources of visible lights that can emit high levels of short-wavelength visible light (blue region in the light spectrum). Prolonged exposure to high-energy blue light, heat dissipation from cell phone, friction, trapped sweat and oil, accumulation of dust, and increased bacterial growth can cause cell phone acne. Management of cell phone acne from prevention to combination therapy based on the results of the evaluation of the severity of acne is needed.
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15
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Fungal Infections among Psoriatic Patients: Etiologic Agents, Comorbidities, and Vulnerable Population. Autoimmune Dis 2021; 2021:1174748. [PMID: 34567800 PMCID: PMC8461225 DOI: 10.1155/2021/1174748] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 08/25/2021] [Accepted: 09/08/2021] [Indexed: 11/18/2022] Open
Abstract
Background Psoriasis is a chronic inflammatory disorder of the skin and joint, affecting nearly 2-3% of the general population. It is assumed that imbalance between the types of natural microflora can accelerate the onset of the disease. Some fungi can play the role of superantigens and prolong chronic inflammation in the skin of psoriatic patients. The aim of the present investigation was to identify fungal species isolated from patients with psoriasis. Methods From March 2016 to May 2019, 289 patients with prior diagnosis of psoriasis were included in this survey. Direct microscopy with potassium hydroxide (KOH 10%), culture, urea hydrolysis, hair perforation test, and growth on rice grains were used to identify clinical isolates, phenotypically. For molecular identification of Candida species and Malassezia species, PCR-RFLP and PCR-sequencing were used, respectively. Results Forty-six out of 289 psoriatic patients had fungal infections (15.9%). Dermatophytes (54.3%), Candida spp. (19.5%), Malassezia spp. (15.2%), Aspergillus spp. (6.5%), and Fusarium spp. (4.3%) were the causative agents of fungal infections. Among Malassezia and Candida species, M. restricta (10.8%) and C. glabrata (8.7%) were the most prevalent species, respectively. Conclusion Our findings suggested that fungal pathogens, particularly dermatophytes, may play an important role in the pathogenicity of psoriasis. Also, due to the high rate of yeast colonization in the clinical samples of psoriatic patients, concomitant use of anti-inflammatory drugs and antifungals may represent an effective therapeutic approach for better management of chronic lesions among these patients. Mycological tests should be applied to indicate the incidence of fungal diseases in psoriatic patients.
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16
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Delftia acidovorans secretes substances that inhibit the growth of Staphylococcus epidermidis through TCA cycle-triggered ROS production. PLoS One 2021; 16:e0253618. [PMID: 34214099 PMCID: PMC8253425 DOI: 10.1371/journal.pone.0253618] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 06/08/2021] [Indexed: 12/22/2022] Open
Abstract
The proportion of Staphylococcus aureus in the skin microbiome is associated with the severity of inflammation in the skin disease atopic dermatitis. Staphylococcus epidermidis, a commensal skin bacterium, inhibits the growth of S. aureus in the skin. Therefore, the balance between S. epidermidis and S. aureus in the skin microbiome is important for maintaining healthy skin. In the present study, we demonstrated that the heat-treated culture supernatant of Delftia acidovorans, a member of the skin microbiome, inhibits the growth of S. epidermidis, but not that of S. aureus. Comprehensive gene expression analysis by RNA sequencing revealed that culture supernatant of D. acidovorans increased the expression of genes related to glycolysis and the tricarboxylic acid cycle (TCA) cycle in S. epidermidis. Malonate, an inhibitor of succinate dehydrogenase in the TCA cycle, suppressed the inhibitory effect of the heat-treated culture supernatant of D. acidovorans on the growth of S. epidermidis. Reactive oxygen species production in S. epidermidis was induced by the heat-treated culture supernatant of D. acidovorans and suppressed by malonate. Further, the inhibitory effect of the heat-treated culture supernatant of D. acidovorans on the growth of S. epidermidis was suppressed by N-acetyl-L-cysteine, a free radical scavenger. These findings suggest that heat-resistant substances secreted by D. acidovorans inhibit the growth of S. epidermidis by inducing the production of reactive oxygen species via the TCA cycle.
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17
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Yousefi A, Karbalaei M, Keikha M. Impact of Streptococcus pyogenes infection in susceptibility to psoriasis: A systematic review and meta-analysis. World J Meta-Anal 2021; 9:309-316. [DOI: 10.13105/wjma.v9.i3.309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/24/2021] [Accepted: 06/17/2021] [Indexed: 02/06/2023] Open
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18
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Yadav M, Sardana I, Sharma A, Sharma N, Nagpal K, Malik P. Emerging Pathophysiological Targets of Psoriasis for Future Therapeutic Strategies. Infect Disord Drug Targets 2021; 20:409-422. [PMID: 31288731 DOI: 10.2174/1871526519666190617162701] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 04/04/2019] [Accepted: 04/13/2019] [Indexed: 12/28/2022]
Abstract
Psoriasis is a chronic autoimmune skin disorder which involves complex interactions between genes, keratinocytes, T-cells and inflammatory cells. It affects 2-3% population worldwide. Molecular biology and cellular immunology of psoriasis, when linked with biotechnology and genetic studies can help researchers to understand the pathophysiology of psoriasis. T-cells activation, keratinocyte hyperproliferation, and angiogenesis are the core mechanisms entailed in the development of psoriasis lesion. Investigators are trying to overcome the challenges of complex pathophysiology pathways involved in this disorder. The different possible hypotheses for its pathophysiology such as growth factors, enzymes, inflammation, and genetic factors mediated pathophysiology have been described in the present review paper in detail. Clinically available drugs only control the symptoms of psoriasis but are not effective for the treatment of the disorder completely and are also associated with some side effects such as itching, renal disorders, hematologic, nonmelanoma skin cancer, pulmonary, gastrointestinal toxicity, etc. This paper made an effort to understand the pathophysiological targets, discuss the research done so far and the treatments available for the effective management of psoriasis.
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Affiliation(s)
- Monu Yadav
- Department of Pharmaceutical Sciences, Chaudhary Bansi Lal University, Bhiwani-127021, Haryana, India
| | - Ishu Sardana
- Department of Pharmaceutical Sciences, Chaudhary Bansi Lal University, Bhiwani-127021, Haryana, India
| | - Amarjeet Sharma
- Department of Pharmaceutical Sciences, Chaudhary Bansi Lal University, Bhiwani-127021, Haryana, India
| | - Nidhi Sharma
- Shri Baba Mastnath Institute of Pharmaceutical Science and Research, Rohtak -124001, Haryana, India
| | - Kalpana Nagpal
- Amity Institute of Pharmacy, Amity University Noida- 201313, Uttar Pradesh, India
| | - Paramjeet Malik
- Department of Pharmaceutical Sciences, Chaudhary Bansi Lal University, Bhiwani-127021, Haryana, India
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19
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Effect of commonly used cosmetic preservatives on skin resident microflora dynamics. Sci Rep 2021; 11:8695. [PMID: 33888782 PMCID: PMC8062602 DOI: 10.1038/s41598-021-88072-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 04/08/2021] [Indexed: 01/15/2023] Open
Abstract
Human skin is populated by various microorganisms, the so-called microbiota, such as bacteria, viruses, yeasts, fungi, and archaea. The skin microbiota is in constant contact with the surrounding environment which can alter its eubiotic state. Recently it has been also observed that the application of cosmetic products can alter the balance of the skin microbiota. This effect may be attributed to many factors including the residual activity of the preservatives on the skin. In the present work, we studied the effect of eleven preservatives commonly found in cosmetic products on Propionibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus in vitro using 3D skin models and culture-dependent methods. Also, the effect on Histone deacetylase 3 (HDAC3) has been investigated. Among tested combinations, three resulted as the best suitable for restoring a pre-existing dysbiosis since they act moderately inhibiting C. acnes and strongly S. aureus without simultaneously inhibiting the growth of S. epidermidis. The other four combinations resulted as the best suitable for use in topical products for skin and scalp in which it is necessary to preserve the eubiosis of the microbiota. Some of the tested were also able to increase HDAC3 expression. Taking together these data highlight the role of preservatives of skin resident microflora dynamics and could provide a reference for correctly choice preservatives and dosage in cosmetic formulations to preserve or restore homeostasis of skin microbiota.
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20
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Zhou H, Shi L, Ren Y, Tan X, Liu W, Liu Z. Applications of Human Skin Microbiota in the Cutaneous Disorders for Ecology-Based Therapy. Front Cell Infect Microbiol 2020; 10:570261. [PMID: 33194808 PMCID: PMC7641908 DOI: 10.3389/fcimb.2020.570261] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 09/18/2020] [Indexed: 12/18/2022] Open
Abstract
The skin represents the exterior interface between the human body with the environment while providing a home to trillions of the commensal microorganisms—collectively referred to as the skin microbiota. These microbes that coexist in an established balance play a pivotal role in the protection of cutaneous health and the orchestration of skin homeostasis. However, the well-controlled but delicate balance can be perturbed by alterations in the skin microbial communities, namely, dysbiosis, often due to commensals defeated by pathogens competing for space and nutrients, which leads to the occurrence of multiple cutaneous disorders. In view of this, the analysis of skin microbiota constituents in skin diseases is crucial for defining the role of commensal microbes and treatment of skin diseases. Emerging evidence shows that the ecology-based therapy of microbial transplantation has been proven as a valid therapeutic strategy for cutaneous disorders caused by skin microbial dysbiosis. Although its mechanism is not well-understood, there are already some applications for ecology-based therapy with the aim of correcting the imbalances on the cutaneous ecosystem. In this review, we summarize the interactions between dysbiosis and the cutaneous disorders, including homeostasis and dysbiosis of skin microbiota, microbial composition in skin diseases, and the mechanisms and applications of reversing or ameliorating the dysbiosis by the targeted manipulation of the skin microbiota, which may contribute to aid development of therapeutic modality for ecology-based therapy.
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Affiliation(s)
- Hong Zhou
- College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Linlin Shi
- College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Yuanyuan Ren
- College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Xi Tan
- College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Liu
- College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.,National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, China
| | - Zhi Liu
- College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.,National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, China
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21
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Esmael A, Hassan MG, Amer MM, Abdelrahman S, Hamed AM, Abd-raboh HA, Foda MF. Antimicrobial activity of certain natural-based plant oils against the antibiotic-resistant acne bacteria. Saudi J Biol Sci 2020; 27:448-455. [PMID: 31889869 PMCID: PMC6933203 DOI: 10.1016/j.sjbs.2019.11.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 11/09/2019] [Accepted: 11/10/2019] [Indexed: 01/12/2023] Open
Abstract
The unceasing emerging of multidrug-resistant bacteria imposes a global foremost human health threat and discovery of new alternative remedies are necessity. The use of plant essential oil in the treatment of many pathogenic bacteria is promising. Acne vulgaris is the most common skin complaint that fears many people about their aesthetic appearance. In this work we investigated the antibacterial activity of some plant oils against acne-inducing bacteria. Three bacterial isolates were identified from Egypt, biochemically and by means of 16s rRNA gene typing, and were designated as Staphylococcus aureus EG-AE1, Staphylococcus epidermidis EG-AE2 and Cutibacterium acnes EG-AE1. Antibiotic susceptibility test showed resistance of the isolates to at least six antibiotics, yet they are still susceptible to the last resort Vancomycin. In vitro investigations of eleven Egyptian plant oils, identified tea tree and rosemary oils to exhibit antibacterial activity against the antibiotic-resistant acne isolates. Inhibition zones of 15 ± 0.5, 21.02 ± 0.73 and 20.85 ± 0.76 mm was detected when tea tree oil applied against the above-mentioned bacteria respectively, while inhibition zones of 12.5 ± 1.5, 15.18 ± 0.38 and 14.77 ± 0.35 mm were detected by rosemary oils. Tea tree and rosemary oils exhibited bacteriostatic and bactericidal activity against all the strains with MICs/MBCs ranging between 39-78 mg/L for tea tree oil and 39-156 mg/L for rosemary oil. All the isolates were killed after 4 and 6 h upon growing with 200 mg/L of tea tree and rosemary oils, respectively. Additionally, gas chromatography mass spectrometry (GC/MS) profiling identified and detected a variable number of antimicrobial compounds in both oils.
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Affiliation(s)
- Ahmed Esmael
- State Key Laboratory of Agricultural Microbiology, College of Plant Science and Technology, College of Life Science and Technology, College of Science, Huazhong Agricultural University, Wuhan 430070, China
- Botany and Microbiology Department, Faculty of Science, Benha University, Qalubiya Governorate 13511, Egypt
| | - Mervat G. Hassan
- Botany and Microbiology Department, Faculty of Science, Benha University, Qalubiya Governorate 13511, Egypt
| | - Mahmoud M. Amer
- Botany and Microbiology Department, Faculty of Science, Benha University, Qalubiya Governorate 13511, Egypt
| | - Soheir Abdelrahman
- Clinical Pathology Department, Faculty of Medicine, Benha University, Qalubiya Governorate 13511, Egypt
| | - Ahmed M. Hamed
- Dermatology Department, Faculty of Medicine, Benha University, Qalubiya Governorate 13511, Egypt
| | - Hagar A. Abd-raboh
- Botany and Microbiology Department, Faculty of Science, Benha University, Qalubiya Governorate 13511, Egypt
| | - Mohamed F. Foda
- State Key Laboratory of Agricultural Microbiology, College of Plant Science and Technology, College of Life Science and Technology, College of Science, Huazhong Agricultural University, Wuhan 430070, China
- Department of Biochemistry, Faculty of Agriculture, Benha University, Moshtohor, Toukh 13736, Egypt
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22
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Edslev SM, Clausen ML, Agner T, Stegger M, Andersen PS. Genomic analysis reveals different mechanisms of fusidic acid resistance in Staphylococcus aureus from Danish atopic dermatitis patients. J Antimicrob Chemother 2019; 73:856-861. [PMID: 29253168 PMCID: PMC5890767 DOI: 10.1093/jac/dkx481] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Accepted: 11/21/2017] [Indexed: 12/16/2022] Open
Abstract
Background Staphylococcus aureus skin colonization is common in patients with atopic dermatitis (AD) and is associated with risk of skin infections. AD patients therefore often receive antibiotic treatments, including topical treatment with fusidic acid, which have been associated with resistance development. Objectives To examine the prevalence of antibiotic resistance in S. aureus isolated from Danish AD patients, with a primary focus on fusidic acid resistance and the genetic mechanisms that underlie it. Methods One hundred and thirty-eight S. aureus isolates collected from lesional skin (n = 54), non-lesional skin (n = 27) and anterior nares (n = 57) from 71 adult AD patients were included in the study. Isolates were tested for susceptibility to 17 selected antibiotics. S. aureus whole-genome sequences were used to examine the genetic determinants of fusidic acid resistance (fusA or fusE mutations or carriage of fusB or fusC genes). Results One hundred and nine isolates (79%) were resistant to at least one of the tested antibiotics, with the most prevalent resistances being to penicillin (55%), fusidic acid (41%) and erythromycin (11%). The primary genetic mechanisms of fusidic acid resistance were carriage of fusC (57%) or mutations in fusA (38%). The most prevalent S. aureus lineage was ST1 (23%). All ST1 isolates carried fusC. Conclusions S. aureus fusidic acid resistance, caused by either fusA mutations or fusC gene carriage, is a major concern among AD patients. Resistant S. aureus might spread from the patients to the community, indicating the need to reduce the use of fusidic acid in the treatment of AD.
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Affiliation(s)
- Sofie Marie Edslev
- Bacteria, Parasites and Fungi, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark
| | - Maja-Lisa Clausen
- Department of Dermatology, Bispebjerg University Hospital, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark
| | - Tove Agner
- Department of Dermatology, Bispebjerg University Hospital, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark
| | - Marc Stegger
- Bacteria, Parasites and Fungi, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark
| | - Paal Skytt Andersen
- Bacteria, Parasites and Fungi, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.,Department of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, 1870 Frederiksberg, Denmark
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23
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Wawrzycki B, Pietrzak A, Grywalska E, Krasowska D, Chodorowska G, Roliński J. Interleukin-22 and Its Correlation with Disease Activity in Plaque Psoriasis. Arch Immunol Ther Exp (Warsz) 2019; 67:103-108. [PMID: 30291393 PMCID: PMC6420473 DOI: 10.1007/s00005-018-0527-5] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 09/17/2018] [Indexed: 02/07/2023]
Abstract
Psoriasis is a chronic debilitating skin disease with an estimated prevalence reaching 2% of the worldwide population. Psoriatic disease is driven by a network of complicated reciprocal interactions among innate and adaptive mechanisms of immune system with structural components of the skin. Interleukin (IL)-22 mediates keratinocyte proliferation and epidermal hyperplasia, inhibits terminal differentiation of keratinocytes, and induces the production of antimicrobial proteins. The aim of this study was the assessment of IL-22 levels and its correlation with disease activity in plaque psoriasis. The study group included 64 patients with mild, moderate and severe psoriasis. Control group was composed of 24 sex- and age-matched healthy volunteers. IL-22 concentration was assessed in supernatants of T-cell cultures as well as in the plasma of study and control group with the use of ELISA method. Statistical analysis showed that concentration of IL-22 in cultures exposed to staphylococcal enterotoxin B was significantly higher than in control samples (p = 0.005) and cultures treated with IL-12 (p = 0.005). Patients with psoriasis presented significantly higher concentrations of IL-22 than healthy individuals (p = 0.0000001). In conclusion, IL-22 may collaborate with other soluble factors and cells together forming inflammatory circuits that otherwise exist as constitutive or inducible pathways in normal skin and become pathologically amplificated in psoriasis. Targeting IL-22 may be promising as a potential therapeutic for plaque psoriasis.
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Affiliation(s)
- Bartłomiej Wawrzycki
- Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Lublin, Poland
| | - Aldona Pietrzak
- Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Lublin, Poland
| | - Ewelina Grywalska
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Chodzki 4a, 20-093, Lublin, Poland.
| | - Dorota Krasowska
- Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Lublin, Poland
| | - Grażyna Chodorowska
- Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Lublin, Poland
| | - Jacek Roliński
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Chodzki 4a, 20-093, Lublin, Poland
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24
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Gannesen AV, Lesouhaitier O, Racine PJ, Barreau M, Netrusov AI, Plakunov VK, Feuilloley MGJ. Regulation of Monospecies and Mixed Biofilms Formation of Skin Staphylococcus aureus and Cutibacterium acnes by Human Natriuretic Peptides. Front Microbiol 2018; 9:2912. [PMID: 30619105 PMCID: PMC6296281 DOI: 10.3389/fmicb.2018.02912] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Accepted: 11/13/2018] [Indexed: 12/28/2022] Open
Abstract
Staphylococcus aureus and Cutibacterium acnes are common representatives of the human skin microbiome. However, when these bacteria are organized in biofilm, they could be involved in several skin disorders such as acne or psoriasis. They inhabit in hollows of hair follicles and skin glands, where they form biofilms. There, they are continuously exposed to human hormones, including human natriuretic peptides (NUPs). We first observed that the atrial natriuretic peptide (ANP) and the C-type natriuretic peptide (CNP) have a strong effect S. aureus and C. acnes biofilm formation on the skin. These effects are significantly dependent on the aero-anaerobic conditions and temperature. We also show that both ANP and CNP increased competitive advantages of C. acnes toward S. aureus in mixed biofilm. Because of their temperature-dependent effects, NUPs appear to act as a thermostat, allowing the skin to modulate bacterial development in normal and inflammatory conditions. This is an important step toward understanding how human neuroendocrine systems can regulate the cutaneous microbial community and should be important for applications in fundamental sciences, medicine, dermatology, and cosmetology.
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Affiliation(s)
- Andrei Vladislavovich Gannesen
- Department of Microbiology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia
- Laboratory of Petroleum Microbiology, Winogradsky Institute of Microbiology, Research Center of Biotechnology, Russian Academy of Sciences, Moscow, Russia
- Laboratory of Microbiology Signals and Microenvironment, EA4312, University of Rouen Normandy, Évreux, France
| | - Olivier Lesouhaitier
- Laboratory of Microbiology Signals and Microenvironment, EA4312, University of Rouen Normandy, Évreux, France
| | - Pierre-Jean Racine
- Laboratory of Microbiology Signals and Microenvironment, EA4312, University of Rouen Normandy, Évreux, France
| | - Magalie Barreau
- Laboratory of Microbiology Signals and Microenvironment, EA4312, University of Rouen Normandy, Évreux, France
| | - Alexander I. Netrusov
- Department of Microbiology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia
| | - Vladimir K. Plakunov
- Laboratory of Petroleum Microbiology, Winogradsky Institute of Microbiology, Research Center of Biotechnology, Russian Academy of Sciences, Moscow, Russia
| | - Marc G. J. Feuilloley
- Laboratory of Microbiology Signals and Microenvironment, EA4312, University of Rouen Normandy, Évreux, France
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25
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Lesouhaitier O, Clamens T, Rosay T, Desriac F, Louis M, Rodrigues S, Gannesen A, Plakunov VK, Bouffartigues E, Tahrioui A, Bazire A, Dufour A, Cornelis P, Chevalier S, Feuilloley MGJ. Host Peptidic Hormones Affecting Bacterial Biofilm Formation and Virulence. J Innate Immun 2018; 11:227-241. [PMID: 30396172 PMCID: PMC6738206 DOI: 10.1159/000493926] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 09/10/2018] [Accepted: 09/10/2018] [Indexed: 12/25/2022] Open
Abstract
Bacterial biofilms constitute a critical problem in hospitals, especially in resuscitation units or for immunocompromised patients, since bacteria embedded in their own matrix are not only protected against antibiotics but also develop resistant variant strains. In the last decade, an original approach to prevent biofilm formation has consisted of studying the antibacterial potential of host communication molecules. Thus, some of these compounds have been identified for their ability to modify the biofilm formation of both Gram-negative and Gram-positive bacteria. In addition to their effect on biofilm production, a detailed study of the mechanism of action of these human hormones on bacterial physiology has allowed the identification of new bacterial pathways involved in biofilm formation. In this review, we focus on the impact of neuropeptidic hormones on bacteria, address some future therapeutic issues, and provide a new view of inter-kingdom communication.
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Affiliation(s)
- Olivier Lesouhaitier
- Laboratory of Microbiology Signals and Microenvironment, LMSM EA 4312, Normandy University, University of Rouen Normandy, Evreux, France,
| | - Thomas Clamens
- Laboratory of Microbiology Signals and Microenvironment, LMSM EA 4312, Normandy University, University of Rouen Normandy, Evreux, France
| | - Thibaut Rosay
- Laboratory of Microbiology Signals and Microenvironment, LMSM EA 4312, Normandy University, University of Rouen Normandy, Evreux, France
| | - Florie Desriac
- Laboratory of Microbiology Signals and Microenvironment, LMSM EA 4312, Normandy University, University of Rouen Normandy, Evreux, France
| | - Mélissande Louis
- Laboratory of Microbiology Signals and Microenvironment, LMSM EA 4312, Normandy University, University of Rouen Normandy, Evreux, France
| | - Sophie Rodrigues
- Laboratory of Microbiology Signals and Microenvironment, LMSM EA 4312, Normandy University, University of Rouen Normandy, Evreux, France
| | - Andrei Gannesen
- Laboratory of Microbiology Signals and Microenvironment, LMSM EA 4312, Normandy University, University of Rouen Normandy, Evreux, France
- Winogradsky Institute of Microbiology, Research Center of Biotechnology of RAS, Moscow, Russian Federation
- Lomonosov Moscow State University, Moscow, Russian Federation
| | - Vladimir K Plakunov
- Winogradsky Institute of Microbiology, Research Center of Biotechnology of RAS, Moscow, Russian Federation
| | - Emeline Bouffartigues
- Laboratory of Microbiology Signals and Microenvironment, LMSM EA 4312, Normandy University, University of Rouen Normandy, Evreux, France
| | - Ali Tahrioui
- Laboratory of Microbiology Signals and Microenvironment, LMSM EA 4312, Normandy University, University of Rouen Normandy, Evreux, France
| | - Alexis Bazire
- Laboratoire de Biotechnologie et Chimie Marines EA 3884, IUEM, Université de Bretagne-Sud (UBL), Lorient, France
| | - Alain Dufour
- Laboratoire de Biotechnologie et Chimie Marines EA 3884, IUEM, Université de Bretagne-Sud (UBL), Lorient, France
| | - Pierre Cornelis
- Laboratory of Microbiology Signals and Microenvironment, LMSM EA 4312, Normandy University, University of Rouen Normandy, Evreux, France
| | - Sylvie Chevalier
- Laboratory of Microbiology Signals and Microenvironment, LMSM EA 4312, Normandy University, University of Rouen Normandy, Evreux, France
| | - Marc G J Feuilloley
- Laboratory of Microbiology Signals and Microenvironment, LMSM EA 4312, Normandy University, University of Rouen Normandy, Evreux, France
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26
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Chang HW, Yan D, Singh R, Liu J, Lu X, Ucmak D, Lee K, Afifi L, Fadrosh D, Leech J, Vasquez KS, Lowe MM, Rosenblum MD, Scharschmidt TC, Lynch SV, Liao W. Alteration of the cutaneous microbiome in psoriasis and potential role in Th17 polarization. MICROBIOME 2018; 6:154. [PMID: 30185226 PMCID: PMC6125946 DOI: 10.1186/s40168-018-0533-1] [Citation(s) in RCA: 198] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 08/13/2018] [Indexed: 05/10/2023]
Abstract
BACKGROUND Psoriasis impacts 1-3% of the world's population and is characterized by hyper-proliferation of keratinocytes and increased inflammation. At the molecular level, psoriasis is commonly driven by a Th17 response, which serves as a major therapeutic target. Microbiome perturbations have been associated with several immune-mediated diseases such as atopic dermatitis, asthma, and multiple sclerosis. Although a few studies have investigated the association between the skin microbiome and psoriasis, conflicting results have been reported plausibly due to the lack of standardized sampling and profiling protocols, or to inherent microbial variability across human subjects and underpowered studies. To better understand the link between the cutaneous microbiota and psoriasis, we conducted an analysis of skin bacterial communities of 28 psoriasis patients and 26 healthy subjects, sampled at six body sites using a standardized protocol and higher sequencing depth compared to previous studies. Mouse studies were employed to examine dermal microbial-immune interactions of bacterial species identified from our study. RESULTS Skin microbiome profiling based on sequencing the 16S rRNA V1-V3 variable region revealed significant differences between the psoriasis-associated and healthy skin microbiota. Comparing the overall community structures, psoriasis-associated microbiota displayed higher diversity and more heterogeneity compared to healthy skin bacterial communities. Specific microbial signatures were associated with psoriatic lesional, psoriatic non-lesional, and healthy skin. Specifically, relative enrichment of Staphylococcus aureus was strongly associated with both lesional and non-lesional psoriatic skin. In contrast, Staphylococcus epidermidis and Propionibacterium acnes were underrepresented in psoriatic lesions compared to healthy skin, especially on the arm, gluteal fold, and trunk. Employing a mouse model to further study the impact of cutaneous Staphylcoccus species on the skin T cell differentiation, we found that newborn mice colonized with Staphylococcus aureus demonstrated strong Th17 polarization, whereas mice colonized with Staphylococcus epidermidis or un-colonized controls showed no such response. CONCLUSION Our results suggest that microbial communities on psoriatic skin is substantially different from those on healthy skin. The psoriatic skin microbiome has increased diversity and reduced stability compared to the healthy skin microbiome. The loss of community stability and decrease in immunoregulatory bacteria such as Staphylococcus epidermidis and Propionibacterium acnes may lead to higher colonization with pathogens such as Staphylococcus aureus, which could exacerbate cutaneous inflammation along the Th17 axis.
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Affiliation(s)
- Hsin-Wen Chang
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA
| | - Di Yan
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA
- Cleveland Clinic Lerner College of Medicine, Cleveland, OH, 44106, USA
| | - Rasnik Singh
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA
- Department of Internal Medicine, Yale University, New Haven, CT, 06520, USA
| | - Jared Liu
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA
| | - Xueyan Lu
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA
- Dermatology Department, Peking University Third Hospital, Beijing, China
| | - Derya Ucmak
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA
- Department of Dermatology, Dicle University School of Medicine, 21280, Diyarbakır, Turkey
| | - Kristina Lee
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA
| | - Ladan Afifi
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA
- University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Douglas Fadrosh
- Division of Gastroenterology, University of California, San Francisco, San Francisco, CA, 94143, USA
| | - John Leech
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA
| | - Kimberly S Vasquez
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA
| | - Margaret M Lowe
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA
| | - Michael D Rosenblum
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA
| | | | - Susan V Lynch
- Division of Gastroenterology, University of California, San Francisco, San Francisco, CA, 94143, USA
| | - Wilson Liao
- Department of Dermatology, University of California, San Francisco, CA, 94115, USA.
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27
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Chen YE, Fischbach MA, Belkaid Y. Skin microbiota-host interactions. Nature 2018; 553:427-436. [PMID: 29364286 DOI: 10.1038/nature25177] [Citation(s) in RCA: 437] [Impact Index Per Article: 62.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Accepted: 11/28/2017] [Indexed: 12/23/2022]
Abstract
The skin is a complex and dynamic ecosystem that is inhabited by bacteria, archaea, fungi and viruses. These microbes-collectively referred to as the skin microbiota-are fundamental to skin physiology and immunity. Interactions between skin microbes and the host can fall anywhere along the continuum between mutualism and pathogenicity. In this Review, we highlight how host-microbe interactions depend heavily on context, including the state of immune activation, host genetic predisposition, barrier status, microbe localization, and microbe-microbe interactions. We focus on how context shapes the complex dialogue between skin microbes and the host, and the consequences of this dialogue for health and disease.
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Affiliation(s)
- Y Erin Chen
- Department of Dermatology, University of California San Francisco, San Francisco, California, USA.,Department of Bioengineering and ChEM-H, Stanford University, Stanford, California, USA
| | - Michael A Fischbach
- Department of Bioengineering and ChEM-H, Stanford University, Stanford, California, USA
| | - Yasmine Belkaid
- NIAID Microbiome Program, National Institute of Allergy and Infectious Disease, NIH, Bethesda, Maryland, USA.,Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, NIH, Bethesda, Maryland, USA
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28
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Pietrzak A, Grywalska E, Socha M, Roliński J, Franciszkiewicz-Pietrzak K, Rudnicka L, Rudzki M, Krasowska D. Prevalence and Possible Role of Candida Species in Patients with Psoriasis: A Systematic Review and Meta-Analysis. Mediators Inflamm 2018; 2018:9602362. [PMID: 29853795 PMCID: PMC5960518 DOI: 10.1155/2018/9602362] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 04/08/2018] [Indexed: 12/15/2022] Open
Abstract
Although fungal colonization is implicated in the pathogenesis of psoriasis, its prevalence remains unclear. The aim of this systematic review and meta-analysis was to provide an overview on the prevalence of Candida species in patients with psoriasis. We searched databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and http://clinicaltrials.gov) to identify studies involving subjects of any age with an established diagnosis of psoriasis and healthy controls, who were tested for carriage of Candida spp. on the skin or mucosal membranes (or saliva and stool), or presented with clinical candidiasis with microbiologically confirmed etiology. We identified nine cross-sectional studies including a total of 1038 subjects with psoriasis (psoriatics) and 669 controls. We found Candida species detection rates for psoriatics were significantly higher than those in the controls, especially in the oral mucosa milieux. These results suggest psoriasis may be one of the systemic diseases that predispose to oral Candida spp. carriage and infection.
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Affiliation(s)
- Aldona Pietrzak
- Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Ul. Radziwillowska 13, 20-080 Lublin, Poland
| | - Ewelina Grywalska
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Ul. Chodźki 4a, 20-093 Lublin, Poland
| | - Mateusz Socha
- Department of Internal Medicine and Cardiology, First Military Clinical Hospital with the Outpatient Clinic, Al. Racławickie 23, 20-048 Lublin, Poland
| | - Jacek Roliński
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Ul. Chodźki 4a, 20-093 Lublin, Poland
| | | | - Lidia Rudnicka
- Department of Dermatology, Medical University of Warsaw, Ul. Koszykowa 82a, 02-008 Warsaw, Poland
| | - Marcin Rudzki
- Chair and Department of Jaw Orthopaedics, Medical University of Lublin, Ul. Karmelicka 7, 20-081 Lublin, Poland
| | - Dorota Krasowska
- Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Ul. Radziwillowska 13, 20-080 Lublin, Poland
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29
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Nguyen CT, Sah SK, Zouboulis CC, Kim TY. Inhibitory effects of superoxide dismutase 3 on Propionibacterium acnes-induced skin inflammation. Sci Rep 2018; 8:4024. [PMID: 29507345 PMCID: PMC5838256 DOI: 10.1038/s41598-018-22132-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 02/06/2018] [Indexed: 12/22/2022] Open
Abstract
Propionibacterium acnes is a well-known commensal bacterium that plays an important role in the pathogenesis of acne and chronic inflammatory skin disease. In this study, we investigated the effect of superoxide dismutase 3 (SOD3) on P. acnes- or peptidoglycan (PGN)-induced inflammation in vitro and in vivo. Our data demonstrated that SOD3 suppressed toll-like receptor-2 (TLR-2) expression in P. acnes- or PGN-treated keratinocytes and sebocytes. Moreover, we found that SOD3 suppressed the expressions of phosphorylated nuclear factor-κB (NF-κB) and p38 in P. acnes- or PGN-treated cells. SOD3 also exhibited an anti-inflammatory role by reducing the expression of inflammasome-related proteins (NLRP3, ASC, caspase-1) and inhibiting the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8. In addition, SOD3 reduced lipid accumulation and expression of lipogenic regulators in P. acnes-treated sebocytes. Recombinant SOD3-treated wild-type mice and SOD3 transgenic mice, which were subcutaneously infected with P. acnes, showed tolerance to inflammation through reducing inflammatory cell infiltration in skin, ear thickness, and expression of inflammatory mediators. Our result showed that SOD3 could suppress the inflammation through inhibition of TLR2/p38/NF-κB axis and NLRP3 inflammasome activation. Therefore, SOD3 could be a promising candidate for treatment of P. acnes-mediated skin inflammation.
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Affiliation(s)
- Cuong Thach Nguyen
- Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, 137-040, South Korea
| | - Shyam Kishor Sah
- Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, 137-040, South Korea
| | - Christos C Zouboulis
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany
| | - Tae-Yoon Kim
- Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, 137-040, South Korea.
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30
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Hwang YF, Wu NY, Lee PY. Koebner phenomenon induced by failed revisional orthopedic surgery but remitted with bone union: A case report. Medicine (Baltimore) 2017; 96:e8138. [PMID: 29019882 PMCID: PMC5662305 DOI: 10.1097/md.0000000000008138] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
RATIONALE Trauma or surgical incision might cause Koebner phenomenon (KP) in patients with cutaneous diseases, but seldom studies reported KP induced by repeated orthopedic surgery. PATIENT CONCERNS The 22-year-old man did not have any prior histories of cutaneous diseases. Two months after the revision surgery for nonunion of the left femoral shaft fracture, KP was noted by psoriasis presented at the surgical scar, left thigh, scalp, and trunk. Phototherapy and topical treatments were prescribed but the effect was limited. DIAGNOSIS KP induced by failed revisional orthopedic surgery. INTERVENTIONS Because of implant failure, he underwent the second revision surgery, which was performed on the previous scar surrounded and covered by psoriatic plaques. OUTCOMES After the second revision surgery successfully corrected the orthopedic problem, the psoriatic lesion remitted along with the bone union. LESSONS In a patient having KP, to perform an operation on psoriatic lesion sites was safe and the surgical wound could heal well. The most important to treat KP induced by orthopedic surgery might be the underlying bone stability.
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Affiliation(s)
| | - Nai-Yuan Wu
- Research Assistant Center, Show-Chwan Memorial Hospital, Changhua
- Institute of Biomedical Informatics, National Yang-Ming University, Taipei
| | - Pei-Yuan Lee
- Department of Orthopedics
- Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan
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