"Pseudo-Beijing": evidence for convergent evolution in the direct repeat region of Mycobacterium tuberculosis

Fenner, Lukas; Malla, Bijaya; Ninet, Béatrice; Dubuis, Olivier; Stucki, David; Borrell, Sonia; Huna, Thembela; Bodmer, Thomas; Egger, Matthias; Gagneux, Sebastien (2011). "Pseudo-Beijing": evidence for convergent evolution in the direct repeat region of Mycobacterium tuberculosis. PLoS ONE, 6(9), e24737. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0024737

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Background Mycobacterium tuberculosis has a global population structure consisting of six main phylogenetic lineages associated with specific geographic regions and human populations. One particular M. tuberculosis genotype known as “Beijing” has repeatedly been associated with drug resistance and has been emerging in some parts of the world. “Beijing” strains are traditionally defined based on a characteristic spoligotyping pattern. We used three alternative genotyping techniques to revisit the phylogenetic classification of M. tuberculosis complex (MTBC) strains exhibiting the typical “Beijing” spoligotyping pattern. Methods and Findings MTBC strains were obtained from an ongoing molecular epidemiological study in Switzerland and Nepal. MTBC genotyping was performed based on SNPs, genomic deletions, and 24-loci MIRU-VNTR. We identified three MTBC strains from patients originating from Tibet, Portugal and Nepal which exhibited a spoligotyping patterns identical to the classical Beijing signature. However, based on three alternative molecular markers, these strains were assigned to Lineage 3 (also known as Delhi/CAS) rather than to Lineage 2 (also known as East-Asian lineage). Sequencing of the RD207 in one of these strains showed that the deletion responsible for this “Pseudo-Beijing” spoligotype was about 1,000 base pairs smaller than the usual deletion of RD207 in classical “Beijing” strains, which is consistent with an evolutionarily independent deletion event in the direct repeat (DR) region of MTBC. Conclusions We provide an example of convergent evolution in the DR locus of MTBC, and highlight the limitation of using spoligotypes for strain classification. Our results indicate that a proportion of “Beijing” strains may have been misclassified in the past. Markers that are more phylogenetically robust should be used when exploring strain-specific differences in experimental or clinical phenotypes.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

UniBE Contributor:

Fenner, Lukas and Egger, Matthias

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:21

Last Modified:

05 Dec 2014 20:13

Publisher DOI:

10.1371/journal.pone.0024737

PubMed ID:

21935448

Web of Science ID:

000295321800057

BORIS DOI:

10.7892/boris.7305

URI:

https://boris.unibe.ch/id/eprint/7305 (FactScience: 212503)

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