Isoniazid and rifampicin resistance-associated mutations in Mycobacterium tuberculosis isolates from Yangon, Myanmar: implications for rapid molecular testing.
OBJECTIVE
To evaluate the frequency and nature of mutations in genes associated with resistance to rifampicin and isoniazid in Mycobacterium tuberculosis isolates collected from Yangon, Myanmar.


METHODS
Ninety-six isoniazid-resistant M. tuberculosis isolates, including 29 multidrug-resistant isolates, were analysed for mutations in the rpoB, katG, inhA, oxyR and ahpC genes.


RESULTS
Mutations in the rpoB gene were detected in 25 (86.2%) of the 29 rifampicin-resistant isolates. Of the 96 isoniazid-resistant isolates, 61 (63.5%) had mutations in codon 315 of the catalase-peroxidase-encoding gene (katG). Mutations in codon 315 were observed at a higher frequency in the multidrug-resistant isolates than in the isoniazid-resistant isolates (86.2% versus 53.7%, respectively, P = 0.003). Mutations in the oxyR-ahpC promoter region and in the inhA gene were observed in 14.6% and 2.1% of the isolates, respectively. Genotyping performed on the 96 M. tuberculosis isolates revealed a total of 94 different genotyping patterns. A distinct genotypic pattern was found in 92 isolates, whereas 4 isolates belonged to two clusters with identical genotypes, suggesting that the majority of the isolates were not from an outbreak of a single drug-resistant clone.


CONCLUSIONS
This study provides the first molecular characterization of isoniazid- and rifampicin-resistant M. tuberculosis isolates from Myanmar and gives information on the molecular basis for rifampicin and isoniazid drug resistance in M. tuberculosis. The study generates useful information for the development of potential rapid molecular drug susceptibility tests.
Valvatne
Håvard
H
Section of Microbiology and Immunology, The Gade Institute, University of Bergen, N-5021 Bergen, Norway.
Syre
Heidi
H
Kross
Martijn
M
Stavrum
Ruth
R
Ti
Ti
T
Phyu
Sabai
S
Grewal
Harleen M S
HM
D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D015373:Bacterial Typing Techniques; D002374:Catalase / Q000235:genetics; D016000:Cluster Analysis; D012321:DNA-Directed RNA Polymerases; D024881:Drug Resistance, Bacterial; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000379:methods; D020125:Mutation, Missense; D002052:Myanmar; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D012293:Rifampin / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D014376:Tuberculosis / Q000175:diagnosis / Q000382:microbiology*
D000995:Antitubercular Agents; D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; D012321:DNA-Directed RNA Polymerases; D007538:Isoniazid; D012293:Rifampin