Focused review on dual inhibition of quorum sensing and efflux pumps: A potential way to combat multi drug resistant Staphylococcus aureus infections

Staphylococcus aureus is a common cause of skin infections, food poisoning and severe life-threatening infections. Methicillin-Resistant Staphylococcus aureus (MRSA) is known to cause chronic nosocomial infections by virtue of its multidrug resistance and biofilm formation mechanisms. The antimicrobial resistance owned by S. aureus is primarily due to efflux pumps and formation of microbial biofilms. These drug resistant, sessile and densely packed microbial communities possess various mechanisms including quorum sensing and drug efflux. Quorum sensing is a cooperative physiological process which is used by bacterial cells for social interaction and signal transduction in biofilm formation whereas efflux of drugs is derived by efflux pumps. Apart from their significant role in multidrug resistance, efflux pumps also contribute to transporting cell signalling molecules and due to their occurrence; we face the frightening possibility that we will enter the pre-antibiotic era soon. Compounds that modulate efflux pumps are also known as efflux pump inhibitors (EPI's) that act in a synergistic manner and potentiate the antibiotics efficacy which has been considered as a promising approach to encounter bacterial resistance. EPIs inhibit the mechanism of drug efflux s as well as transport of quorum sensing signalling molecules which are the supreme contributors of miscellaneous virulence factors. This review presents an accomplishments of the recent investigations allied to efflux pump inhibitors against S. aureus and also focus on related correspondence between quorum sensing system and efflux pump inhibitors in terms of S. aureus and MRSA biofilms that may open a new avenue for controlling MRSA infections.