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Monocaprin, Monolaurin, and Monomyristin Eradicate Staphylococcus aureus Persister Cells Through Membrane Disruption
1Department of Forest Products and Biotechnology, Kookmin University, Seoul 02707, Republic of Korea.
Abstract:
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.
Insights
Monoglycerides like monolaurin effectively kill Staphylococcus aureus persister cells by damaging their cell membranes. This discovery offers new strategies against persistent bacterial infections.
Area of Science:
- Microbiology
- Biochemistry
Background:
- Staphylococcus aureus persister cells pose a significant challenge to antimicrobial therapy due to their antibiotic tolerance.
- Chronic and recurrent infections are often linked to these resilient bacterial populations.
- The potential of monoglycerides as membrane-active antimicrobials is recognized, but their impact on persister cells requires further investigation.
Purpose of the Study:
- To evaluate the efficacy of monocaprin, monolaurin, and monomyristin against Staphylococcus aureus persister cells.
- To elucidate the mechanism of action of these monoglycerides on persister cell viability.
- To explore the role of membrane disruption in the anti-persister activity.
Main Methods:
- Assessing the anti-persister activity of three monoglycerides against S. aureus.
- Employing membrane permeability assays to investigate cellular effects.
- Utilizing fluorescence microscopy for mechanistic analysis.
- Testing the influence of Tween 80 on monoglyceride activity and membrane permeability.
Main Results:
- Monocaprin, monolaurin, and monomyristin demonstrated reduced survival of S. aureus persister cells.
- Monolaurin showed the highest anti-persister activity; monocaprin and monomyristin exhibited concentration-dependent bactericidal effects.
- Monoglycerides increased membrane permeability, leading to compromised persister cell viability.
- Tween 80 counteracted the bactericidal effects and membrane permeability increase, confirming membrane disruption as the mode of action.
Conclusions:
- The antibacterial action of monocaprin, monolaurin, and monomyristin against S. aureus is intrinsically linked to membrane damage.
- These membrane-active monoglycerides show promise as novel agents for eradicating S. aureus persister cells.
- Targeting bacterial membranes presents a viable strategy against persistent S. aureus infections.
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