PHENOTYPIC AND GENOTYPIC CHARACTERISTICS OF ISONIAZID RESISTANCE IN MYCOBACTERIUM TUBERCULOSIS

Tuberculosis (TB) is a single infectious disease, caused by Mycobacterium tuberculosis and represent high mortality of people in many countries. It is estimated that over three million people die a year of tuberculosis. Isoniazid (isonicotinic acid hydrazide; INH) is one of the structurally simplest primary chemotherapeutic and prophylactic drugs used to treat M. tuberculosis since 1952. INH is the most widely administered to tuberculosis patients than any other drug, and among the antituberculosis drugs, it is against INH emergence of resistance have been frequently reported. INHresistance is apparently controlled by a complex genetic system that involves several genes, namely, katG, inhA, oxyRahpC. The two predominant mutations of katG, and those most referred to, are found within codons 315 and 463. The primary target of activated INH is an NADH-dependent enoyl-acyl carrier protein reductase, designated InhA. The aim of this study is to confirm M. tuberculosis to PCR targeting MPB64 gene and IS6110 and to determine isoniazid resistance by in vitro phenotypic resistant to the drug by Broth Microdilution method and resistance associated mutation by DNA isolation, PCR amplification, DNA sequencing analysis to detect mutations within katG gene and inhA gene of the isolates to search further why the isolate become isoniazid-resistant. The study revealed INH-resistant isolates for which the INH MICs were 0.19 to 3.125 mg/ml had polymorphism in codon 463 (R463L), and insertions at 323, 719 and 720 with these mutations conferring low level INH resistance.