Molecular diagnosis of drug-resistant tuberculosis

ABSTRACT

The worldwide emergence and spread of multidrug- resistant [MDR] strains of Mycobacterium tuberculosis has adverse effects on tuberculosis [TB] control programs. The goal of this paper is to describe the advances made in the understanding of the molecular basis of M. tuberculosis resistance to first-line anti-TB drugs, and to discuss the potential of molecular methods in early diagnosis of drug-resistant TB. Molecular methods such as DNA sequencing, polymerase chain reaction, DNA hybridization and restriction fragment length polymorphism have been used to identify/detect mutations in gene-encoding proteins or rRNA which are targets for the first-line anti-TB drugs. High level resistance to rifampin [RIF], isoniazid [INH], pyrazinamide [PZA], ethambutol [EMB], and streptomycin [STR] is caused by mutations in rpoB, katG, pncA, embB and rpsL/rrs genes, respectively. The most common mutations conferring high level resistance to RIF, INH, EMB and STR have been identified in rpoB, katG, embB and rpsLgenes, respectively. Molecular methods to detect the most frequent mutations in the gene encoding functions that are targets for first-line anti-TB drugs have provided encouraging results for early diagnosis of MDR-TB