Project description:Background: Atopic dermatitis (AD) is a common inflammatory skin disease with a TH2 immune polarity and is often colonized with Staphylococcus aureus. Despite recent advances in understanding Staphylococcus species infection and the impact of polar TH cytokines on the skin, the interactions between these factors in AD pathology are poorly understood. Methods: AD-related key immune biomarkers were measured by quantitative real-time PCR in human keratinocytes exposed heat-killed S. epidermidis or S. aureus with/without polar T-cell derived cytokines such as IFN-γ (TH1), IL-4/IL-13 (TH2), and IL-22 (TH22). Further analysis was performed by RNA-sequencing to define broader responses in both Staphylococcus species and polar cytokines. The similarity of gene expression patterns in AD skin lesions and stimulated keratinocytes was evaluated by gene-set variation analysis (GSVA). Results: Gene expression analysis exhibited distinct immune responses in keratinocytes depending on individual bacterial or polar cytokine exposure. Besides, numerous genes were synergistically upregulated by the combination exposure of bacteria and polar TH cytokines. Moreover, GSVA revealed that combined exposure of S. aureus and IL-4 + IL-13 exhibited significantly higher correlations with a genomic signature of AD skin lesions than their single exposure or combinations of other polar TH cytokines. Conclusions: Our findings provide novel insights into AD-related transcriptional activation and illustrate a potentially novel pathogenic function of S. aureus and IL-4/IL-13 interactions in AD.
Project description:Staphylococcus aureus and Staphylococcus epidermidis, two Gram-positive bacteria commonly found in the human skin microbiota, form biofilms that contribute to skin dysbiosis and play a key role in conditions like acne and atopic dermatitis. The Calcitonin Gene-Related Peptide (CGRP) is a human peptide involved in skin inflammation. We previously showed that CGRP enhances the virulence of S. epidermidis MFP04 and that the DnaK chaperone protein is significantly overexpressed in the secretome of CGRP-activated virulent S. epidermidis. In this study, we explored a potential new role of S. epidermidis DnaK in biofilm formation in both S. aureus and S. epidermidis. We showed that recombinant S. epidermidis DnaK differentially affects biofilm formation, whether in two skin commensal staphylococcal strains (S. aureus MFP03 and S. epidermidis MFP04) or in a clinical S. aureus strain (CIP 107093). In the clinical strain S. aureus CIP 107093, biofilm formation was most strongly inhibited. This inhibition involves both the Substrate-Binding Domain and the Nucleotide-Binding Domain of DnaK. Proteomic analysis revealed that DnaK alters the S. aureus biofilm proteome, stabilizing proteins involved in protein degradation like ClpP and ETA, while downregulating key regulatory proteins involved in biofilm development such as SaeS and WalK. These results indicate that S. epidermidis DnaK may contribute to the regulation of S. aureus biofilm formation, suggesting a cross-species regulatory role of DnaK within the skin microbiota.
Project description:Atopic dermatitis (AD), the most prevalent chronic inflammatory skin disease in children worldwide, is characterized by skin barrier dysfunction and microbial dysbiosis. Staphylococcus aureus colonizes lesional skin in up to 70% of AD patients, exacerbating inflammation through virulence factors (e.g., enterotoxin B, SplD protease) and biofilm formation, which disrupt the skin barrier and trigger Th2 immune responses. However, existing studies primarily focus on individual virulence factors, leaving the core regulatory mechanisms enabling persistent S. aureus colonization in AD poorly understood.
Project description:Staphylococcus aureus is one of the most important pathogens in humans and animals, multiply resistant strains are increasingly widespread, new agents are needed for the treatment of S. aureus. Rhein, a natural plant product, has potential antimicrobial activity against Staphylococcus aureus. We employed Affymetrix Staphylococcus aureus GeneChipsTM arrays to investigate the global transcriptional profiling of Staphylococcus aureus ATCC25923 treated with rhein. Results provided insight into mechanisms involved in rhein - Staphylococcus aureus interactions. Keywords: rhein response
Project description:The effect of anti-mouse IL-4 and/or anti-mouse IL-13 Kinoid vaccines was assessed in a model of atopic dermatitis. Mice were immunized with IL-4 and/or IL13 Kinoids (or the carrier protein CRM197 alone as control). Atopic dermatitis-like pathology was induced by repeated epicutaneous exposures to house dust mite and the enterotoxin B from Staphylococcus aureus (SEB). Lesional skin biopsies were collected for bulk RNA sequencing analysis.
Project description:Staphylococcus aureus (S. aureus) is an important human and animal pathogen, multiply resistant strains are increasingly widespread, new agents are needed for the treatment of S. aureus. magnolol has potent antimicrobial activity against S. aureus. We employed Affymetrix Staphylococcus aureus GeneChipsTM arrays to investigate the global transcriptional profiling of Staphylococcus aureus ATCC25923 treated with magnolol. Keywords: gene expression array-based, count
Project description:To determine if significant genomic changes are associated with the development of vancomycin intermediate Staphylococcus aureus, genomic DNA microarrays were performed to compare the initial vancomycin susceptible Staphylococcus aureus (VSSA) and a related vancomycin intermediate Staphylococcus aureus (VISA) isolate from five unique patients (five isolate pairs). Keywords: comparative genomic hybridization