Genome-scale metabolic modeling and in silico analysis of opportunistic skin pathogen Cutibacterium acnes

• Published in: Frontiers in cellular and infection microbiology Vol. 13; p. 1099314
• Main Authors: Kim, Su-Kyung, Lee, Minouk, Lee, Yi Qing, Lee, Hyun Jun, Rho, Mina, Kim, Yunkwan, Seo, Jung Yeon, Youn, Sung Hun, Hwang, Seung Jin, Kang, Nae Gyu, Lee, Choong-Hwan, Park, Seo-Young, Lee, Dong-Yup
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 13.07.2023
• Subjects: acne vulgaris; Cellular and Infection Microbiology; Cutibacterium acnes; genome-scale metabolic model; skin microbiome; skin pathogen; Wood-Werkman cycle; acne vulgaris; skin microbiome; Cutibacterium acnes; skin pathogen; Wood-Werkman cycle; genome-scale metabolic model
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2023.1099314

, one of the most abundant skin microbes found in the sebaceous gland, is known to contribute to the development of acne vulgaris when its strains become imbalanced. The current limitations of acne treatment using antibiotics have caused an urgent need to develop a systematic strategy for selectively targeting , which can be achieved by characterizing their cellular behaviors under various skin environments. To this end, we developed a genome-scale metabolic model (GEM) of virulent , CA843, based on the genome information of a relevant strain from ribotype 5 to comprehensively understand the pathogenic traits of in the skin environment. We validated the model qualitatively by demonstrating its accuracy prediction of propionate and acetate production patterns, which were consistent with experimental observations. Additionally, we identified unique biosynthetic pathways for short-chain fatty acids in compared to other GEMs of acne-inducing skin pathogens. By conducting constraint-based flux analysis under endogenous carbon sources in human skin, we discovered that the Wood-Werkman cycle is highly activated under acnes-associated skin condition for the regeneration of NAD, resulting in enhanced propionate production. Finally, we proposed potential anti- targets by using the model-guided systematic framework based on gene essentiality analysis and protein sequence similarity search with abundant skin microbiome taxa.