Isoniazid and rifampicin resistance-associated mutations in Mycobacterium tuberculosis isolates from Yangon, Myanmar: implications for rapid molecular testing

• Published in: Journal of antimicrobial chemotherapy Vol. 64; no. 4; pp. 694 - 701
• Main Authors: Valvatne, Håvard, Syre, Heidi, Kross, Martijn, Stavrum, Ruth, Ti, Ti, Phyu, Sabai, Grewal, Harleen M. S.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.10.2009; Oxford Publishing Limited (England)
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - pharmacology; Bacterial Proteins - genetics; Bacterial Typing Techniques; Biological and medical sciences; Catalase - genetics; Cluster Analysis; DNA-Directed RNA Polymerases; Drug resistance; Drug Resistance, Bacterial; drug susceptibility; Genetics; Genotype; Genotype & phenotype; Humans; Isoniazid - pharmacology; Medical sciences; Microbial Sensitivity Tests - methods; molecular characterization; Mutation; Mutation, Missense; Myanmar; Mycobacterium tuberculosis; Mycobacterium tuberculosis - classification; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Oxidoreductases - genetics; Pharmacology. Drug treatments; Point Mutation; Polymorphism, Restriction Fragment Length; Promoter Regions, Genetic; Rifampin - pharmacology; Sequence Analysis, DNA; Tuberculosis; Tuberculosis - diagnosis; Tuberculosis - microbiology; Myanmar; Asia; Yangon Myanmar; molecular characterization; TB; drug susceptibility; Nucleotide sequence; Drug susceptibility test; Medical screening; Resistance; Antibiotic; Rifampicin; Mycobacterium tuberculosis; Mycobacteriales; Mycobacteriaceae; Bacteria; Genetics; Isolate; Actinomycetes; Antituberculous agent; Protein synthesis inhibitor; Mutation; Antibacterial agent; Isoniazid
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkp292

Objectives 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.