Combating multidrug-resistant (MDR) Staphylococcus aureus infection using terpene and its derivative

Multidrug-resistant (MDR) Staphylococcus aureus represents a major global health issue resulting in a wide range of debilitating infections and fatalities. The slow progression of new antibiotics, limited choices for treatment, and scarcity of new drug approvals create immense obstacles in new drug line development. S. aureus poses a significant public health risk, due to the emergence of methicillin-resistant (MRSA) and vancomycin-resistant strains (VRSA), necessitating novel antibiotics for effective control management. Current studies are delving into the terpenes' potential as an antimicrobial agent, indicating positive prospects as promising substitutes or complementary to conventional antibiotics. Concurrent reactions of terpenes with conventional antibiotics create synergistic effects that significantly enhance antibiotic efficacy. Accumulated evidence has shown that while efflux pump (e.g., NorA, TetK, and MepA) is revealed as an essential defense of S. aureus against antibiotics, terpene and its derivative act as its potent inhibitor, suggesting the promising potential of terpenes in combating those infectious pathogens. Furthermore, pronounced cell membrane disruptive activity and antibiofilm properties by terpenes have been exerted, signifying their significance as promising prevention against microbial pathogenesis and antimicrobial resistance. This review provides an overview of the potential of terpenes and their derivatives in combating S. aureus infections, highlighting their potential mechanisms of action (MOA), synergistic effects with conventional antibiotics, and challenges in clinical translation. The unique properties of terpenes offer an opportunity for their use in developing an exceptional defense strategy against antibiotic-resistant S. aureus.