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Review Article

SRP. 2019; 10(1): s43-s48


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

Faiqah Umar, Mochammad Hatta, Dirayah Rauf Husain, Burhanuddin Bahar, Agussalim Bukhari, Ressy Dwiyanti, Ade Rifka Junita, Muhammad Reza Primaguna.

Abstract
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.

Key words: Antibiotics, drug-resistant, Efflux inhibitors, M. tuberculosis, Verapamil.



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