Evolution of structural fitness and multifunctional aspects of mycobacterial RND family transporters

Abstract

Drug resistance is a major concern due to the evolution and emergence of pathogenic bacterial strains with novel strategies to resist the antibiotics in use. Mycobacterium tuberculosis (Mtb) is one of such pathogens with reported strains, which are not treatable with any of the available anti-TB drugs. This scenario has led to the need to look for some novel drug targets in Mtb, which may be exploited to design effective treatment strategies against the infection. The goal of this review is to discuss one such class of emerging drug targets in Mtb. MmpL (mycobacterial membrane protein large) proteins from Mtb are reported to be involved in multi-substrate transport including drug efflux and considered as one of the contributing factors for the emergence of multidrug-resistant strains. MmpL proteins belong to resistance nodulation division permeases superfamily of membrane transporters, which are viably and pathogenetically important and their inhibition could be lethal for the bacteria.

Keywords: Antibiotics; Drug resistance; Drug targets; Efflux pumps; MmpL; MmpS; Mycobacterium tuberculosis; RND transporters.