Anti-staphylococcal fatty acids: mode of action, bacterial resistance and implications for therapeutic application

Novel strategies to counter multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus are urgently required. The antimicrobial properties of fatty acids (FAs) have long been recognized and offer significant promise as viable alternatives to, or potentiators of, conventional antibiotics. In this review, we examine the interplay between FAs and S. aureus, specifically detailing the underlying molecular mechanisms responsible for FA-mediated inhibition and the counteracting staphylococcal systems evolved to withstand FA onslaught. Finally, we present an update on the recent therapeutic FA applications to combat S. aureus infection, either as a monotherapy or in combination with antibiotics or host-derived antimicrobial peptides. Given the frequency of interaction between FAs and S. aureus during host colonization and infection, understanding FA mode of action and deciphering S. aureus FA resistance strategies are central in rationally designing future anti-staphylococcal FAs and FA-combination therapies.