This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Baker, L. V.
Right arrow Articles by Drobniewski, F. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baker, L. V.
Right arrow Articles by Drobniewski, F. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2005, p. 1455-1464, Vol. 49, No. 4
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.4.1455-1464.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Molecular Analysis of Isoniazid-Resistant Mycobacterium tuberculosis Isolates from England and Wales Reveals the Phylogenetic Significance of the ahpC –46A Polymorphism

L. V. Baker, T. J. Brown, O. Maxwell, A. L. Gibson, Z. Fang, M. D. Yates, and F. A. Drobniewski0*

HPA Mycobacterium Reference Unit, Department of Microbiology, Guy's, King's and St Thomas' School of Medicine, King's College Hospital, London, United Kingdom

Received 20 July 2004/ Returned for modification 19 August 2004/ Accepted 16 November 2004

The present study investigated the prevalence and diagnostic potential of the most commonly reported mutations associated with isoniazid resistance, katG 315Thr, katG 315Asn, inhA –15T, inhA –8A, and the oxyR-ahpC intergenic region, in a population sample of 202 isoniazid-resistant Mycobacterium tuberculosis isolates and 176 randomly selected fully sensitive isolates from England and Wales identified by using a directed oligonucleotide array and limited DNA sequencing. The strains were recovered from patients originating from 29 countries; 41 isolates were multidrug resistant. Mutations affecting katG 315, the inhA promoter, and the oxyR-ahpC intergenic region were found in 62.7, 21.9, and 30% of 169 genotypically distinct isoniazid-resistant isolates, respectively, whereas they were found in 0, 0, and 8% of susceptible strains, respectively. The frequency of mutation at each locus was unrelated to the resistance profile or previous antituberculous drug therapy. The commonest mutation in the oxyR-ahpC intergenic region, ahpC –46A, was present in 23.7% of isoniazid-resistant isolates and 7.5% of susceptible isolates. This proved to be a phylogenetic marker for a subgroup of M. tuberculosis strains originating on the Indian subcontinent, which shared IS6110-based restriction fragment length polymorphism and spoligotype features with the Delhi strain and Central Asian strain CAS1; and this marker is strongly associated with isoniazid resistance and the katG 315Thr mutation. In total, 82.8% of unrelated isoniazid-resistant isolates could be identified by analysis of just two loci: katG 315 and the inhA promoter. Analysis of the oxyR-ahpC intergenic region, although phylogenetically interesting, does not contribute significantly to further identification of isoniazid-resistant isolates.

* Corresponding author. Mailing address: HPA Mycobacterium Reference Unit, Department of Microbiology, Guy's, King's and St Thomas' School of Medicine, King's College Hospital, East Dulwich Grove, London SE22 8QF, United Kingdom. Phone: 44 20 8333 3000. Fax: 44 20 8333 3092. E-mail: francis.drobniewski{at}kcl.ac.uk.

Antimicrobial Agents and Chemotherapy, April 2005, p. 1455-1464, Vol. 49, No. 4
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.4.1455-1464.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bolotin, S., Alexander, D. C., Chedore, P., Drews, S. J., Jamieson, F. (2009). Molecular characterization of drug-resistant Mycobacterium tuberculosis isolates from Ontario, Canada. J Antimicrob Chemother 64: 263-266 [Abstract] [Full Text]  
  • Huang, W.-L., Chen, H.-Y., Kuo, Y.-M., Jou, R. (2009). Performance Assessment of the GenoType MTBDRplus Test and DNA Sequencing in Detection of Multidrug-Resistant Mycobacterium tuberculosis. J. Clin. Microbiol. 47: 2520-2524 [Abstract] [Full Text]  
  • Hazbon, M. H., Motiwala, A. S., Cavatore, M., Brimacombe, M., Whittam, T. S., Alland, D. (2008). Convergent Evolutionary Analysis Identifies Significant Mutations in Drug Resistance Targets of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 52: 3369-3376 [Abstract] [Full Text]  
  • Barnard, M., Albert, H., Coetzee, G., O'Brien, R., Bosman, M. E. (2008). Rapid Molecular Screening for Multidrug-Resistant Tuberculosis in a High-Volume Public Health Laboratory in South Africa. Am. J. Respir. Crit. Care Med. 177: 787-792 [Abstract] [Full Text]  
  • Caws, M., Tho, D. Q., Duy, P. M., Lan, N. T. N., Hoa, D. V., Torok, M. E., Chau, T. T. H., Van Vinh Chau, N., Chinh, N. T., Farrar, J. (2007). PCR-Restriction Fragment Length Polymorphism for Rapid, Low-Cost Identification of Isoniazid-Resistant Mycobacterium tuberculosis. J. Clin. Microbiol. 45: 1789-1793 [Abstract] [Full Text]  
  • Guo, H., Seet, Q., Denkin, S., Parsons, L., Zhang, Y. (2006). Molecular characterization of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis from the USA.. J Med Microbiol 55: 1527-1531 [Abstract] [Full Text]  
  • Brossier, F., Veziris, N., Truffot-Pernot, C., Jarlier, V., Sougakoff, W. (2006). Performance of the Genotype MTBDR Line Probe Assay for Detection of Resistance to Rifampin and Isoniazid in Strains of Mycobacterium tuberculosis with Low- and High-Level Resistance.. J. Clin. Microbiol. 44: 3659-3664 [Abstract] [Full Text]  
  • Hazbon, M. H., Brimacombe, M., Bobadilla del Valle, M., Cavatore, M., Guerrero, M. I., Varma-Basil, M., Billman-Jacobe, H., Lavender, C., Fyfe, J., Garcia-Garcia, L., Leon, C. I., Bose, M., Chaves, F., Murray, M., Eisenach, K. D., Sifuentes-Osornio, J., Cave, M. D., Ponce de Leon, A., Alland, D. (2006). Population Genetics Study of Isoniazid Resistance Mutations and Evolution of Multidrug-Resistant Mycobacterium tuberculosis.. Antimicrob. Agents Chemother. 50: 2640-2649 [Abstract] [Full Text]  
  • Caws, M., Duy, P. M., Tho, D. Q., Lan, N. T. N., Hoa, D. V., Farrar, J. (2006). Mutations Prevalent among Rifampin- and Isoniazid-Resistant Mycobacterium tuberculosis Isolates from a Hospital in Vietnam.. J. Clin. Microbiol. 44: 2333-2337 [Abstract] [Full Text]  
  • Park, H., Song, E. J., Song, E. S., Lee, E. Y., Kim, C. M., Jeong, S. H., Shin, J. H., Jeong, J., Kim, S., Park, Y. K., Bai, G.-H., Chang, C. L. (2006). Comparison of a Conventional Antimicrobial Susceptibility Assay to an Oligonucleotide Chip System for Detection of Drug Resistance in Mycobacterium tuberculosis Isolates.. J. Clin. Microbiol. 44: 1619-1624 [Abstract] [Full Text]  
  • Leung, E. T. Y., Ho, P. L., Yuen, K. Y., Woo, W. L., Lam, T. H., Kao, R. Y., Seto, W. H., Yam, W. C. (2006). Molecular Characterization of Isoniazid Resistance in Mycobacterium tuberculosis: Identification of a Novel Mutation in inhA. Antimicrob. Agents Chemother. 50: 1075-1078 [Abstract] [Full Text]  
  • Lavender, C., Globan, M., Sievers, A., Billman-Jacobe, H., Fyfe, J. (2005). Molecular Characterization of Isoniazid-Resistant Mycobacterium tuberculosis Isolates Collected in Australia. Antimicrob. Agents Chemother. 49: 4068-4074 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»