Mycobacterium tuberculosis efflux pumps: an update

The selection and diffusion of Mycobacterium tuberculosis multidrug-resistant (MDR-TB), extensively drug-resistant (XDR-TB) and, more recently, totally drug-resistant (TDR) strains constitute a serious threat for tuberculosis global control. Mycobacteria, such as M. tuberculosis and Mycobacterium smegmatis, possess several putative drug efflux transporters, but their role in resistance is still a hard topic and needs to be further investigated as resistance to several drugs is usually the result of the combination of independent mutations in genes encoding either the drug target or the enzymes involved in drug activation. However, as the genetic basis of resistance to some antitubercular agents is not fully known for some clinical isolates, we cannot rule out an efflux mechanism in these strains. Several drug efflux transporters have been described in mycobacteria as responsible for resistance to aminoglycosides, chloramphenicol, fluoroquinolones, isoniazid, linezolid, rifampicin, tetracycline and other compounds but most of them were isolated in laboratory rather than in hospitals.