Bacterial Resistance Mechanisms and Inhibitors of Multidrug Efflux Pumps Belonging to the Major Facilitator Superfamily of Solute Transport Systems

Multidrug resistant pathogenic bacteria pose a serious public health concern as their recalcitrant nature enhances treatment failure of infectious diseases. Several molecular mechanisms are responsible for multidrug resistance in bacteria. A major antibacterial resistance mechanism involves active drug efflux, grouped into transporter superfamilies. Of these, the major facilitator superfamily harbors clinically important drug and multidrug efflux pumps and constitutes a large number of transporters that share similarities in protein sequences, three-dimensional protein structures, energy modes, and evolutionary origin. Multidrug efflux pumps of the major facilitator superfamily in bacterial pathogens compromise the efficacy of infectious disease treatments. Thus, inhibition of these antibacterial efflux pumps is critical in order to circumvent drug resistance and potentially restore the clinical utility of infectious disease chemotherapy. This chapter summarizes bacterial resistance systems and multidrug efflux pumps from the major facilitator superfamily and the nature of efflux pump inhibitors.