katG GENE ASSOCIATION WITH ISONIAZID RESISTANCE IN MULTIPLE DRUG RESISTANT TUBERCULOSIS IN PAKISTAN

ABSTRACT

Background:

The unfolding of multi-drug resistant Mycobacterium Tuberculosis (MDR-MTB) constitutes a grave threat to the currentendeavorsfor controlling the tuberculosis outbreak. During TB treatment, the drug-resistance with 1stline drugs likeRifampicin (RIF) and Isoniazid (INH) has to be re-evaluated. It is assumed that gene mutation is underlying etiology for drug resistance during TB treatment. In Isoniazid resistant MTB, researchers have reported point mutation in katG gene at codon 315. The main objective of this study was to evaluate katG gene association with isoniazid (INH) resistance in our population.

Methods:

Sputum specimens from suspected TB were inoculated in LJ Medium after proper decontamination. Identification of the organism colonies growth on slopes was done followed by drug sensitivity analysis. Isolates having resistance to Isoniazid (INH) and Rifampicin (RIF) with or without any other drug resistance were categorized as Multi-drug resistant (MDR). Kit method was used for DNA extraction. Then region from base 2714 to 3232 of katG gene was amplified through PCR followed by sequencing with the help of BLAST- alignment software. 24 Multi Drug Resistant MTB specimens were processed.

Results:

DNA sequence analysis revealed the reported mutation Ser → Thr in katG codon 315 in five samples (21%). In this study, an authentic molecular analysis (test) was developed and validated for identification of INH resistant strains in Pakistani population.

Conclusion:

Our study concludes that mutation of some genes particularly point mutation of katG gene at codon 315 is associated with development of resistance to the drug INH in Multi drug resistant TB.

Keywords:

Isoniazid; Multi-Drug Resistant; Mycobacterium Tuberculosis.

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