Membrane-disrupting medium-chain fatty acids reduce Staphylococcus aureus persister cell survival during antibiotic treatment.

Objectives: 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 analyzed 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.

Conclusion: 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.