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 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:In the present study, we investigated the effect of Cutibacterium acnes on lifespan and susceptibility to infection with Staphylococcus aureus using Caenorhabditis elegans as a model animal. When adult C. elegans were fed C. acnes strains, the lifespan of the animals fed pathogenic C. acnes strain (HM-122) was significantly shorter than that of animals fed OP50 (control). In contrast, the lifespan of the animals fed commensal C. acnes strain (HM-555) was not significantly different from that of animals in the control group. Moreover, the worms fed the commensal C. acnes strain were more resistant to infection with S. aureus. Transcriptional profiling comparing HM-122-, HM-555- and control-fed animals suggested that genes related to “cuticle development involved in collagen and cuticulin-based cuticle molting cycle” were regulated by HM-122, and genes related to “defense response to gram-positive bacterium” were regulated by HM-555.
