USEFULNESS OF MYCOBACTERIUM-TUBERCULOSIS GENOMIC MUTATIONS IN THE GENES KATG AND INHA FOR THE PREDICTION OF ISONIAZID RESISTANCE

SETTING: Mutations in two genes of Mycobacterium tuberculosis, inhA an d katG, are known to correlate with resistance to isoniazid (INH). OBJ ECTIVE: To determine which mutation or mutations are the most predicti ve for INH resistance and the most frequent ones in such isolates. Fur ther, to propose a simple and generally applicable method for their de tection. DESIGN: Codons 94 and 95 in the inhA gene and codons 315 and 463 in the katG gene were characterized in 50 INH-resistant and 12 INH -sensitive isolates from Germany and Sierra Leone. RESULTS:: Mutations in codon 315 of the katG gene were detected in 27 of the INH-resistan t and none of the INH-sensitive isolates. All mutations in this codon altered an AciI restriction enzyme site. No mutations were found in th e investigated codons of the inhA gene. CONCLUSION: We propose that mo st INH resistances can be rapidly predicted by a simple AciI restricti on enzyme digest of a polymerase chain reaction (PCR)-amplified katG f ragment.