JAC Advance Access originally published online on August 26, 2009
Journal of Antimicrobial Chemotherapy 2009 64(4):694-701; doi:10.1093/jac/dkp292
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original research |
Isoniazid and rifampicin resistance-associated mutations in Mycobacterium tuberculosis isolates from Yangon, Myanmar: implications for rapid molecular testing
1 Section of Microbiology and Immunology, The Gade Institute, University of Bergen, N-5021 Bergen, Norway 2 Department of Microbiology and Immunology, Haukeland University Hospital, N-5021 Bergen, Norway 3 National TB Programme, No. 223, Ngu War Street, Ahlone Township, Yangon, Union of Myanmar 4 Novartis Institute for Tropical Diseases, 10 Biopolis Road, 05-01 Chromos Building, Singapore 138670
Received 25 February 2009; returned 21 April 2009; revised 25 May 2009; accepted 19 July 2009
* Corresponding author. Section of Microbiology and Immunology, The Gade Institute, University of Bergen and Haukeland University Hospital, N-5021 Bergen, Norway. Tel: +47-55974929; Fax: +47-55974979; E-mail: Heidi.Syre{at}Gades.uib.no
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.
Keywords: TB , drug susceptibility , molecular characterization
Both authors contributed equally.