Project description:Cutibacterium acnes (C. acnes) is a ubiquitous skin commensal bacterium that is generally well tolerated by the immune system. Different strain-types of C. acnes have been reported to be enriched on patients with acne. To understand if these strain-types contribute to skin inflammation, we generated a library of over 200 C. acnes isolates from skin swabs of healthy and acne subjects and assessed their strain-level identity and inflammatory potential. Phylotype II K-type strains were more frequent on healthy and acne non-lesional skin compared to lesional. Phylotype IA-1 C-type strains were dominant on acne lesional skin but absent from healthy. Measurement of host cytokine responses from C. acnes supernatant revealed neither strain-type nor skin-type association predicted inflammatory potential. However, differential proinflammatory responses were induced from identical strain-types, but these differences were not attributable to protease, short chain fatty acid or porphyrin production. Instead, whole genome sequencing revealed the presence of a linear plasmid in high inflammatory strain-types. Intradermal injection of C. acnes in mouse skin revealed a plasmid-associated inflammatory response in dermal fibroblasts, revealed by single-cell RNA sequencing. We conclude that C. acnes strain-type is not sufficient to predict inflammation but other virulence factors including a plasmid may contribute to disease.
Project description:Recently the membrane vesicles (MVs) production has been observed in Gram-positive bacterium, Cutibacterium acnes (C. acnes). In order to explore the mechanism of antibiotic resistance and the virulent components within the C. acnes-derived MVs, we isolated MVs from the clinical C. acnes, which were sensitive or resistant to antibiotics erythromycin and clindamycin. With the LC-MS/MS method, we detected several lipases, virulent factors and cell division protein differentially expressed between the sensitive and the resistant C. acnes-derived MVs.
Project description:Cutibacterium acnes (C. acnes) is a common skin commensal associated with acne pathogenesis. Here, we investigated the capacity of acne-associated (CA) and healthy skin-associated (CH) C. acnes strains to induce extracellular trap (ET) formation in human neutrophils (NETs) and Th17 cells (TETs) and performed proteomic analyses to define their molecular signatures. NETs displayed a conserved protein profile regardless of the C. acnes strain, whereas TETs exhibited strain-specific proteomic profiles. CA-induced TETs were enriched in inflammatory and extracellular matrix remodeling proteins, while CH-induced TETs showed upregulation of nuclear, mitochondrial, and antimicrobial proteins, including granulysin, granzyme B, and cathepsin C. These findings underscore strain- and cell type-specific regulation of ET formation and suggest that CH-induced TETs may contribute to skin immune homeostasis, whereas CA-induced TETs may promote inflammatory and tissue remodeling responses in acne. Our study reveals a potential mechanism by which skin microbiota differentially modulates Th17 effector programs, ultimately influencing downstream immune activity and skin health.
