Review on Molecular Mechanism of First Line Antibiotic Resistance in Mycobacterium tuberculosis

Tuberculosis (TB) is among the most common infectious diseases and frequent causes of death worldwide claiming many of lives annually. The problem of tuberculosis is hampered by the emergence of multi drug resistant(MDR) and extensively drug resistant (XDR) tuberculosis. Anti-tuberculosis drugs are a two-edged sword. While they destroy pathogenic Mycobacterium tuberculosis they also select for drug resistant bacteria against which those drugs are then ineffective. In contrast to other bacteria, resistance of M. tuberculosis is exclusively associated with chromosomal mutations. Globally, the emergence of multidrug-resistant strains of M. tuberculosis is an increasing problem which adversely affects patient care and public health. The objective of this review is therefore to compile available literatures about the drug resistance mechanisms of M. tuberculosis which gives insight understanding for the development of new therapeutic and diagnostic methods for the management of MDR and XDR tuberculosis infections. Resistance to first line anti-TB drugs has been linked to mutations in at least 10 genes; katG, inhA, ahpC, kasA and ndh for INH resistance; rpoB for RIF resistance, embB for EMB resistance, pncA for PZA resistance and rpsL and rrs for STR resistance. The search for new anti-tuberculosis drugs shall consider new targets which are less susceptible for mutation.