Journal of Antimicrobial Agents

Antimicrobial Compounds of Plant Origin as Efflux Pump Inhibitors: New Avenues for Controlling Multidrug Resistant Pathogens

Abstract

Rao M, Padyana S, Dipin KM, Kumar S, Nayak BB and Varela MF

The emergence of multiple drug resistant pathogenic bacteria has severely constricted the antimicrobial options of treating infectious diseases. One of the powerful mechanisms of antibacterial resistance employed by the antibiotic resistant bacteria is the active extrusion of antimicrobials with the help of membrane transporters known as efflux pumps. Efflux pumps effectively reduce the intracellular concentrations of antimicrobials by their antiporter activity in which antimicrobials are extruded outside the bacterial cell using energy derived from ionic gradient across the cell membrane. While a few efflux pumps are capable of conferring clinical levels of resistance to antibiotics, while many others only marginally increase the minimum inhibitory concentrations (MIC) of antibiotics. However, the role of efflux pumps in gradual development of antibiotic resistance by pathogenic bacteria due to mutations and other molecular mechanisms during the course of antimicrobial therapy is well recognized. The inhibition of active efflux can result in maintenance of an intracellular concentration of antibiotics necessary to inhibit or kill bacteria. Plant-derived compounds have historically been recognized as effective antimicrobial agents. Advances in analytical techniques have enabled purification of natural compounds responsible for efflux pump inhibition and these compounds and their derivatives can act as lead compounds for designing more effective efflux pump inhibitors. Efflux pump inhibition is promising as an effective method of confronting bacterial resistance to antimicrobials either alone or as adjuvants with antibiotics, and thereby restoring the antibacterial efficacy of antibiotics.