The non-clonality of drug resistance in Beijing-genotype isolates of Mycobacterium tuberculosis from the Western Cape of South Africa

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dc.contributor.authorLoerger, Thomas R.
dc.contributor.authorFeng, Yicheng
dc.contributor.authorChen, Xiaohua
dc.contributor.authorDobos, Karen M.
dc.contributor.authorVictor, Thomas C.
dc.contributor.authorStreicher, Elizabeth M.
dc.contributor.authorWarren, Robin M.
dc.contributor.authorGey van Pittius, Nicolaas C.
dc.contributor.authorVan Helden, Paul D.
dc.contributor.authorSacchettini, James C.
dc.date.accessioned2010-12-20T14:16:28Z
dc.date.available2010-12-20T14:16:28Z
dc.date.issued2010-11
dc.date.updated2010-12-20T14:01:53Z
dc.description.abstractBackground. The Beijing genotype of M. tuberculosis is a virulent strain that is disseminating worldwide and has a strong association with drug resistance. In the Western Cape of South Africa, epidemiological studies have identified the R220 cluster of the Beijing genotype as a major contributor to a recent outbreak of drug-resistant tuberculosis. Although the outbreak is considered to be due to clonal transmission, the relationship among drug resistant isolates has not yet been established. Results. To better understand the evolution of drug resistance among these strains, 14 drug-resistant clinical isolates of the Beijing genotype were sequenced by whole-genome sequencing, including eight from R220 and six from a more ancestral Beijing cluster, R86, for comparison. While each cluster shares a distinct resistance mutation for isoniazid, mapping of other drug-resistance mutations onto a phylogenetic tree constructed from single nucleotide polymorphisms shows that resistance mutations to many drugs have arisen multiple times independently within each cluster of isolates. Thus, drug resistance among these isolates appears to be acquired, not clonally derived. This observation suggests that, although the Beijing genotype as a whole might have selective advantages enabling its rapid dissemination, the XDR isolates are relatively less fit and do not propagate well. Although it has been hypothesized that the increased frequency of drug resistance in some Beijing lineages might be caused by a mutator phenotype, no significant shift in synonymous substitution patterns is observed in the genomes. Conclusion. While MDR-TB is spreading by transmission in the Western Cape, our data suggests that further drug resistance (i.e. XDR-TB) at this stage is acquired.en_ZA
dc.description.versionPeer Reviewed
dc.format.extent13 p. : col. ill.
dc.identifier.citationLoerger, TR, Feng, Y, Chen, X, Dobos, KM, Victor, TC, Streicher, EM, Warren, RM, Gey van Pittius, NC, Van Helden, PD & Sacchettini, JC 2010, 'The non-clonality of drug resistance in Beijinggenotype isolates of Mycobacterium tuberculosis from the Western Cape of South Africa', BMC Genomics, 11(1):670.en_ZA
dc.identifier.issn1471-2164
dc.identifier.otherdoi.org/10.1186/1471-2164-11-670
dc.identifier.urihttp://hdl.handle.net/10019.1/5494
dc.language.isoen_ZAen_ZA
dc.language.rfc3066en
dc.publisherBioMed Centralen_ZA
dc.rights.holderLoerger et al.; licensee BioMed Central Ltd.en_ZA
dc.subjectMycobacterium tuberculosisen_ZA
dc.subjectWestern Cape of South Africaen_ZA
dc.subjectBeijing genotypeen_ZA
dc.subjectDrug resistant tuberculosisen_ZA
dc.titleThe non-clonality of drug resistance in Beijing-genotype isolates of Mycobacterium tuberculosis from the Western Cape of South Africaen_ZA
dc.typeArticleen_ZA
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