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Published on: May 15, 2019
Commensal-derived short-chain fatty acids disrupt lipid membrane homeostasis in Staphylococcus aureus
Joshua R Fletcher1,2, Lisa A Hansen3, Richard Martinez1
1Department of Microbiology & Immunology, University of Minnesota, Minneapolis, MN 55455.
Abstract:
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.
Insights
Anaerobic bacteria metabolites, propionate and butyrate, disrupt Staphylococcus aureus metabolism, impairing growth and increasing antimicrobial sensitivity. This impacts pathogen interactions in chronic respiratory infections.
Area of Science:
- Microbiology
- Host-Microbe Interactions
- Metabolic Biochemistry
Background:
- Commensal anaerobic bacteria are abundant in chronic respiratory infections but their role is poorly understood.
- Anaerobes may influence pathogen behavior through nutrient competition and toxic metabolite production.
Purpose of the Study:
- To investigate the impact of anaerobe-derived metabolites on Staphylococcus aureus physiology.
- To elucidate the mechanism by which short-chain fatty acids affect S. aureus fitness and interactions with other pathogens.
Main Methods:
- Analysis of Staphylococcus aureus response to short-chain fatty acids (propionate and butyrate).
- Assessment of branched-chain fatty acid (BCFA) metabolism alterations.
- Evaluation of S. aureus growth, agr quorum sensing system expression, and antimicrobial susceptibility.
- Competition assays between S. aureus and Pseudomonas aeruginosa.
Main Results:
- Propionate and butyrate disrupt S. aureus branched-chain fatty acid (BCFA) metabolism.
- BCFA disruption leads to impaired growth, reduced agr quorum sensing, and increased susceptibility to antimicrobials.
- Altered BCFA metabolism diminishes S. aureus fitness in competition with P. aeruginosa.
Conclusions:
- Anaerobe-derived SCFAs significantly impact S. aureus physiology and fitness.
- Airway microbiome composition and metabolites influence pathogen dynamics in chronic infections.
- SCFAs show potential as sensitizers for traditional antimicrobial agents.
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