Verapamil as an Efflux Inhibitor Against Drug Resistant Mycobacterium Tuberculosis: A Review

Resistance to antituberculosis (anti-TB) drugs is a growing global problem, which is not only related to the high level of HIV co-infection. However, it can also be caused by the presence of multi-, extensively-, and totally drug-resistant Mycobacterium tuberculosis strain, hence the choice of using anti-TB drugs is getting smaller. The mechanism of emergence of drug-resistant bacterial strains is due to the mutation of drug target genes, decreased barrier permeability, and increased efflux rate. Drug resistance due to increased efflux pump activity is caused by overexpression of efflux pump genes, and amino acid substitution in protein, making efflux pump activity more efficient. Both mechanisms cause a reduction in intracellular anti-TB concentration so that the organism becomes less susceptible to the drug component. Number of studies have been conducted to explore components that can inhibit the action of bacterial efflux pump. Verapamil is a blocker of Ca2+, a prototype of the phenylalkalylamine group that has the potential to inhibit the efflux pump of M. tuberculosis bacteria to be more susceptible to anti-TB drugs both in vivo and in vitro. The study of new components or a combination of adjuvant components and anti-TB drugs to treat drug-resistant M. tuberculosis infections is the main goal in the development of more effective TB treatment strategies.