Efflux Pumps in Mycobacteria: Antimicrobial Resistance, Physiological Functions, and Role in Pathogenicity

Abstract

The emergence of multidrug and extensively drug-resistant tuberculosis represents a major threat to the control of the disease. Antimicrobial drug resis-tance in Mycobacterium tuberculosis is not merely a consequence of the occur-rence of gene mutations in the drug targets but a balance between the acquisition of mutations and drug effl ux. The low permeability of the mycobacterial cell wall acts synergistically with active drug effl ux pumps, and this combined mechanism may particularly constitute the fi rst step for the development of drug resistance. Besides drug effl ux, effl ux pumps also have physiological functions in the bacteria, and their expression is subjected to tight regulation in response to multiple environmental and physiological signals. Understanding the mechanisms underlying drug effl ux, effl ux pump regulation and their contribution for pathogenicity not only enables the devel-opment of more rapid and accurate tools for the guidance of antituberculosis ther-apy but also provides knowledge for the development of new therapeutic strategies.