associated mutations in Mycobacterium tuberculosis isolates from ...

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Jan 7, 2011 - from Yangon, Myanmar: implications for rapid molecular testing. J Antimicrob Chemother 2009; 64: 694–701. 2 Baker L, Brown T, Maxwell O et ...
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The frequencies of both mutations, and hence the frequencies of the corresponding lineages in the study by Valvatne et al.,1 are in line with spoligotyping data from another study that analysed strains from the same year and sample location, and found that 4.8% and 48.4% of isolates belonged to the CAS lineage and the EAI lineage, respectively.6

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References 1 Valvatne H, Syre H, Kross M et al. Isoniazid and rifampicin resistance-associated mutations in Mycobacterium tuberculosis isolates from Yangon, Myanmar: implications for rapid molecular testing. J Antimicrob Chemother 2009; 64: 694–701. 2 Baker L, Brown T, Maxwell O et al. Molecular analysis of isoniazid-resistant Mycobacterium tuberculosis isolates from England and Wales reveals the phylogenetic significance of the ahpC 246A polymorphism. Antimicrob Agents Chemother 2005; 49: 1455 –64. 3 Comas I, Homolka S, Niemann S et al. Genotyping of genetically monomorphic bacteria: DNA sequencing in Mycobacterium tuberculosis highlights the limitations of current methodologies. PLoS One 2009; 4: e7815. 4 Baker L, Brown T, Maiden M et al. Silent nucleotide polymorphisms and a phylogeny for Mycobacterium tuberculosis. Emerg Infect Dis 2004; 10: 1568– 77. 5 Galagan J, Sisk P, Stolte C et al. TB database 2010: overview and update. Tuberculosis (Edinb) 2010; 90: 225–35. 6 Phyu S, Stavrum R, Lwin T et al. Predominance of Mycobacterium tuberculosis EAI and Beijing lineages in Yangon, Myanmar. J Clin Microbiol 2009; 47: 335–44.

*Corresponding author. E-mail: [email protected]

Keywords: TB, drug susceptibility, molecular characterization

Sir, We thank Ko¨ser et al.1 for their valuable comments on our paper2 and note with interest the association of specific single nucleotide polymorphisms (SNPs) with Mycobacterium tuberculosis strain lineages; the mutation at position –46 in the oxyR – ahpC intergenic region with the Central Asian (CAS) lineage and the C to T mutation in oxyR with East African –Indian (EAI) lineage strains. This corroborates some of our own recent observations3 in a study conducted in a country that neighbours Myanmar (India), where we showed by SNP analysis of the pncA gene (conferring resistance to pyrazinamide) a CAS lineage-specific silent mutation, S65S, which is observed for the majority of CAS lineage isolates. There seems to be a somewhat mixed view with regard to the role of the frequent mutation in the oxyR– ahpC intergenic region at position –46. In a study by Baker et al.,4 among 378 strains, the oxyR– ahpC mutation was present in 23.7% of isoniazid-resistant isolates and 7.5% of susceptible isolates. Although a phylogenetic marker for a subgroup of M. tuberculosis strains originating on the Indian subcontinent (CAS), this marker is strongly associated with isoniazid resistance and the katG 315Thr mutation.4 Indeed, oxyR is a pseudogene, and in our study from Myanmar we interestingly observed that a synonymous polymorphism is more frequently observed in isoniazid-resistant isolates than in multidrug-resistant isolates (P,0.001). This finding needs to be verified in studies from other geographical areas.

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J Antimicrob Chemother 2011 doi:10.1093/jac/dkq514 Advance Access publication 7 January 2011

Isoniazid and rifampicin resistanceassociated mutations in Mycobacterium tuberculosis isolates from Yangon, Myanmar: implications for rapid molecular testing—authors’ response Heidi Syre1,2* and Harleen Grewal1,2 1

Section of Microbiology and Immunology, The Gade Institute, University of Bergen, N-5021 Bergen, Norway; 2Department of Microbiology and Immunology, Haukeland University Hospital, N-5021 Bergen, Norway

References 1 Ko¨ser CU, Summers DK, Archer JAC. Comment on: Isoniazid and rifampicin resistance-associated mutations in Mycobacterium tuberculosis isolates from Yangon, Myanmar: implications for rapid molecular testing. J Antimicrob Chemother 2011; 66: 686–7. 2 Valvatne H, Syre H, Kross M et al. Isoniazid and rifampicin resistance-associated mutations in Mycobacterium tuberculosis isolates from Yangon, Myanmar: implications for rapid molecular testing. J Antimicrob Chemother 2009; 64: 694–701. 3 Stavrum R, Myneedu VP, Arora VK et al. In-depth molecular characterization of Mycobacterium tuberculosis from New Delhi – predominance of drug resistant isolates of the ‘modern’ (TbD12) type. PLoS ONE 2009; 4: e4540. 4 Baker VL, Brown TJ, Maxwell O et al. Molecular analysis of isoniazid-resistant Mycobacterium tuberculosis isolates from England and Wales reveals the phylogenetic significance of the ahpC – 46A polymorphism. Antimicrob Agents Chemother 2005; 49: 1455 –64.

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