Commensal-derived short-chain fatty acids disrupt lipid membrane homeostasis in Staphylococcus aureus .

Autor:	Fletcher JR; Department of Microbiology & Immunology, University of Minnesota, Minneapolis, MN 55455.; Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine, Raleigh, NC 27695., Hansen LA; Department of Microbiology & Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, 14203., Martinez R; Department of Microbiology & Immunology, University of Minnesota, Minneapolis, MN 55455., Freeman CD; Department of Chemistry, University of Georgia, Athens, GA, 30602., Thorns N; Department of Microbiology & Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, 14203., Villareal AR; Department of Microbiology & Immunology, University of Minnesota, Minneapolis, MN 55455., Penningroth MR; Department of Microbiology & Immunology, University of Minnesota, Minneapolis, MN 55455., Vogt GA; Department of Microbiology & Immunology, University of Minnesota, Minneapolis, MN 55455., Tyler M; Department of Otolaryngology, University of Minnesota, Minneapolis, MN, 55455., Hines KM; Department of Chemistry, University of Georgia, Athens, GA, 30602., Hunter RC; Department of Microbiology & Immunology, University of Minnesota, Minneapolis, MN 55455.; Department of Microbiology & Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, 14203.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Aug 12. Date of Electronic Publication: 2024 Aug 12.
DOI:	10.1101/2024.08.12.607382
Abstrakt:	The role of commensal anaerobic bacteria in chronic respiratory infections is unclear, yet they can exist in abundances comparable to canonical pathogens in vivo . Their contributions to the metabolic landscape of the host environment may influence pathogen behavior by competing for nutrients and creating inhospitable conditions via toxic metabolites. Here, we reveal a mechanism by which the anaerobe-derived short chain fatty acids (SCFAs) propionate and butyrate negatively affect Staphylococcus aureus physiology by disrupting branched chain fatty acid (BCFA) metabolism. In turn, BCFA impairment results in impaired growth, diminished expression of the agr quorum sensing system, as well as increased sensitivity to membrane-targeting antimicrobials. Altered BCFA metabolism also reduces S. aureus fitness in competition with Pseudomonas aeruginosa , suggesting that airway microbiome composition and the metabolites they produce and exchange directly impact pathogen succession over time. The pleiotropic effects of these SCFAs on S. aureus fitness and their ubiquity as metabolites in animals also suggests that they may be effective as sensitizers to traditional antimicrobial agents when used in combination.
Databáze:	MEDLINE
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