The Major Facilitator Superfamily and Antimicrobial Resistance Efflux Pumps of the ESKAPEE Pathogen Staphylococcus aureus
Jerusha Stephen, Fathima Salam, Manjusha Lekshmi, Sanath Kumar, Manuel F. Varela
Abstract
The ESKAPEE bacterial pathogen Staphylococcus aureus has posed a serious public health concern for centuries. Throughout its evolutionary course, S. aureus has developed strains with resistance to antimicrobial agents. The bacterial pathogen has acquired multidrug resistance, causing, in many cases, untreatable infectious diseases and raising serious public safety and healthcare concerns. Amongst the various mechanisms for antimicrobial resistance, integral membrane proteins that serve as secondary active transporters from the major facilitator superfamily constitute a chief system of multidrug resistance. These MFS transporters actively export structurally different antimicrobial agents from the cells of S. aureus. This review article discusses the S. aureus-specific MFS multidrug efflux pump systems from a molecular mechanistic perspective, paying particular attention to structure–function relationships, modulation of antimicrobial resistance mediated by MFS drug efflux pumps, and direction for future investigation.