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:External insults can cause immune activation in immune cells, resulting in persistent molecular changes that can lead to innate immune memory (IIM) changes in these cells. This study investigated the potential for cellular reprogramming in response to Cutibacterium acnes in keratinocytes. We exposed normal human epidermal keratinocytes obtained by mammoplasty (NHEK-B) or abdominoplasty (NHEK-A) to C. acnes, followed by stimulation with Pam3CSK4 to assess immune activation and cellular responses. In NHEK-B cells, C. acnes and Pam3CSK4 treatment induced trained immunity-type responses, with higher expression of selected immune target genes, and a diminished response compared with that in nontrained but Pam3CSK4-induced NHEK-A cells. Total transcriptome analysis delineated regional differences, with the activation of immune-related pathways in NHEK-B cells and increased skin development in NHEK-A cells. We detected differences in metabolic regulation, and utilizing pharmacological inhibitors, we demonstrated the necessity of the optimal regulation of histone acetylation and DNA methylation for the aforementioned changes. This study demonstrated that C. acnes triggers IIM-like processes in keratinocytes, characterized by signaling, epigenetic, and metabolic reprogramming that influences cellular responses to subsequent stimuli. The observation that analogous insults might elicit skin region specific responses offers novel insights into the etiology and mechanisms underlying common inflammatory skin diseases.
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:The importance of the impact of human hormones on commensal microbiota and microbial biofilms is established in lots of studies. In the present investigation, we studied the proteome of biofilms and planktonic cultures of skin actinobacterium Cutibacterium acnes. In our investigation, we tested the effect of epinephrine in concentrations 5 nM (normal blood level) and 5 µM (1000-fold higher) on 72 h biofilms and planktonic cultures in comparison with controls without the hormone administration. Also, we compared the samples treated with epinephrine in different concentrations. Also, we investigated the differences between planktonic cultures and biofilms and how the hormone influences those differences. The present database contains the raw data of proteins changes in their concentrations in described conditions.
Project description:The pathogenesis of acne vulgaris is multifactorial and is influenced by the presence of Cutibacterium acnes. This study investigated how different strains of C. acnes, associated with either healthy skin (CH) or acne-prone skin (CA), selectively modulate the function of three dendritic cell (DC) subtypes: Langerhans cell-derived (LCDC), monocyte-derived (moDCs), and myeloid (mDCs). Our findings revealed that all DC subtypes secreted varying levels of TGF-β, IL-1β, IL-6, IL-12p70, and IL-23 in response to C. acnes stimulation. Notably, moDCs exhibited the highest cytokine secretion in response to CA-ribotypes, indicating their potent immune responsiveness. Conversely, LCDCs were the least responsive, regardless of the ribotypes. Principal component (PCA) and gene ontology (GO) analysis of bulk RNA sequencing data of DCs exposed to C. acnes identified extensive transcriptional changes, particularly in immune response pathways. moDCs showed the most pronounced transcriptional changes, aligning with their high cytokine secretion levels. Additionally, we identified specific genes upregulated by CA-ribotypes, with notable differences among the DC types, highlighting the unique contributions of each DC subtype to the skin's immune defense mechanisms against C. acnes. Overall, our study underscores the complexity of DC responses in the skin's immune environment and provides valuable insights into their roles in acne.
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.