Characterization of ndh gene of isoniazid resistant and susceptible Mycobacterium tuberculosis isolates from Brazil

Resistance in Mycobacterium tuberculosis to isoniazid (INH) is caused by mutations in the catalase-peroxi-dase gene (katG), and within the inhA promoter and/or in structural gene. A small percentage ( ~ 10%) of INH-resistant strains do not present mutations in both of these loci. Other genes have been associated with INH resistance including the gene encoding for NADH dehydrogenase (ndh). Here we report the detection of two ndh locus mutations (CGT to TGT change in codon 13 and GTG to GCG change in codon 18) by analyzing 23 INH-resistant and in none of 13 susceptible isolates from Brazilian tuberculosis patients. We also detected two isolates without a mutation in ndh, or any of the other INH resistance-associated loci examined, suggesting the existence of additional, as yet to be described, INH resistance mechanisms. Key words: Mycobacterium tuberculosis- NADH dehydrogenase gene- isoniazid resistance Isoniazid (INH) has been a first-line drug for tuber-culosis treatment for many years and yet its mechanism of action remains only partially understood (Rozwarski et al. 1998, Heym et al. 1999). Molecular studies have demonstrated that mutations in katG and inhA (regula-tory and structural regions) confer resistance to INH i