Monocaprin, Monolaurin, and Monomyristin Eradicate Staphylococcus aureus Persister Cells Through Membrane Disruption

Background/Objectives: Staphylococcus aureus persister cells significantly undermine antimicrobial therapy through their transient antibiotic tolerance, contributing to chronic and recurrent infections. Although monoglycerides have shown potential as membrane-active antimicrobial agents, their effect on persister cells remains insufficiently understood. Methods: In this study, we evaluated the anti-persister activities of monocaprin, monolaurin, and monomyristin against S. aureus persister cells. Mechanistic analyses were performed using membrane permeability assays and fluorescence microscopy. Results: All three monoglycerides reduced persister cell survival, with varying degrees depending on fatty acid chain length. Monolaurin exhibited the greatest anti-persister activity, whereas monocaprin and monomyristin exerted concentration-dependent bactericidal effects. Mechanistic analyses revealed that these compounds increased membrane permeability, thereby compromising cell viability in S. aureus persister cells. In contrast, Tween 80 attenuated both the bactericidal effect and the increase in membrane permeability, supporting the involvement of membrane disruption in their mode of action. Conclusions: The antibacterial activity of monocaprin, monolaurin, and monomyristin against S. aureus is closely associated with membrane damage. These membrane-active monoglycerides represent promising antimicrobial candidates for the eradication of S. aureus persister cells.