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Membrane-disrupting medium-chain fatty acids reduce Staphylococcus aureus persister cell survival during antibiotic
Yena Seo1, Minjun Kim1, Dae-Youn Kim1
1Department of Forest Products and Biotechnology, College of Science and Technology, Kookmin University, Seoul, Republic of Korea.
Objective:
Eliminating persister cells is essential to improve treatment of chronic infections and to limit the emergence of resistant strains. Medium-chain fatty acids (MCFAs) are widely used in cosmetics and antibiotic ointments where Staphylococcus aureus is a common commensal. This study evaluated the potential of MCFAs to eradicate S. aureus persister cells and investigated their mechanisms of action.
Methods:
The bactericidal activity of MCFAs against S. aureus persisters was assessed after treatment with three antibiotics - ciprofloxacin, oxacillin, and tobramycin. Membrane permeability was analysed by fluorescence microscopy and ATP leakage assays.
Results:
Octanoic, decanoic, and lauric acids at 10, 1, and 0.1 mM, respectively, significantly reduced antibiotic-surviving cells in persister-enriched populations, independent of antibiotic class. In contrast, myristic acid did not eliminate persisters up to 10 mM, although it was active against exponentially growing cells. The bactericidal activity of MCFAs increased with chain length from octanoic to lauric acid. Killing correlated with enhanced membrane permeability, whereas changes in membrane fluidity or transmembrane potential were not predictive.
Conclusions:
MCFAs, particularly lauric acid at low concentrations, effectively eradicate S. aureus persisters and may enhance skin health when incorporated into topical products. Their activity increases with chain length and is linked to membrane permeability disruption. Myristic acid, while effective against metabolically active cells, is ineffective against persisters, highlighting physiological differences between growth states.
Insights
Medium-chain fatty acids (MCFAs) effectively kill Staphylococcus aureus persister cells, which are difficult to treat in chronic infections. Lauric acid showed the most potent activity by disrupting bacterial membranes.
Area of Science:
- Microbiology
- Dermatology
- Infectious Diseases
Background:
- Persister cells are dormant subpopulations of bacteria that survive antibiotic treatment, contributing to chronic infections and antibiotic resistance.
- Medium-chain fatty acids (MCFAs) are commonly found in topical products and possess antimicrobial properties.
- Staphylococcus aureus is a significant human pathogen, frequently causing persistent infections.
Purpose of the Study:
- To evaluate the efficacy of MCFAs in eradicating Staphylococcus aureus persister cells.
- To investigate the mechanism of action by which MCFAs eliminate persister cells.
Main Methods:
- Assessed the bactericidal activity of various MCFAs against S. aureus persisters pre-treated with antibiotics (ciprofloxacin, oxacillin, tobramycin).
- Analyzed membrane permeability using fluorescence microscopy and ATP leakage assays.
- Investigated changes in membrane fluidity and transmembrane potential.
Main Results:
- Octanoic, decanoic, and lauric acids significantly reduced antibiotic-surviving S. aureus persisters at low millimolar concentrations.
- MCFA bactericidal activity increased with fatty acid chain length (octanoic to lauric acid).
- Killing activity correlated with increased membrane permeability, but not with changes in membrane fluidity or potential.
Conclusions:
- MCFAs, especially lauric acid, are effective agents for eradicating S. aureus persisters, potentially aiding in chronic infection treatment.
- The mechanism involves disruption of bacterial membrane permeability.
- Myristic acid was ineffective against persisters, unlike metabolically active cells, indicating distinct physiological states.
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