Dataset Information

Disclosure of selective advantages in the “modern” sublineage of the Mycobacterium tuberculosis Beijing genotype family by quantitative proteomics.

ABSTRACT: Using two different comparative proteomic approaches we studied the M. tuberculosis Beijing genotype.

INSTRUMENT(S): LTQ FT

ORGANISM(S): Mycobacterium Tuberculosis C

SUBMITTER: Jeroen de Keijzer

LAB HEAD: Peter van Veelen

PROVIDER: PXD000931 | Pride | 2014-07-16

REPOSITORIES: Pride

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Disclosure of selective advantages in the "modern" sublineage of the Mycobacterium tuberculosis Beijing genotype family by quantitative proteomics.

de Keijzer Jeroen J de Haas Petra E PE de Ru Arnoud H AH van Veelen Peter A PA van Soolingen Dick D

Molecular & cellular proteomics : MCP 20140714 10

The Mycobacterium tuberculosis Beijing genotype, consisting of the more ancient (atypical) and modern (typical) emerging sublineage, is one of the most prevalent and genetically conserved genotype families and has often been associated with multidrug resistance. In this study, we employed a 2D-LC-FTICR MS approach, combined with dimethylation of tryptic peptides, to systematically compare protein abundance levels of ancient and modern Beijing strains and identify differences that could be associ ...[more]

PMID: 25022876

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Project description:Background. The Beijing family of Mycobacterium tuberculosis is dominant in countries in East Asia. Genomic polymorphisms are a source of diversity within the M.tuberculosis genome and may account for the variation of virulence among M.tuberculosis isolates. To date there are no studies that have examined the genomic composition of M.tuberculosis isolates from the high TB-burden country, Myanmar. Methodology/Principle findings. Twenty-two M.tuberculosis isolates from Myanmar were screened on whole-genome arrays containing genes from M.tuberculosis H37Rv, M.tuberculosis CDC1551 and M.bovis AF22197. Screening identified 198 deletions or extra regions in the clinical isolates compared to H37Rv. Twenty-two regions differentiated between Beijing and non-Beijing isolates and were verified by PCR on an additional 40 isolates. Six regions (Rv0071-0074 [RD105], Rv1572-1576c [RD149], Rv1585c-1587c[RD149], MT1798-Rv1755c [RD152], Rv1761c [RD152] and Rv0279c) were deleted in Beijing isolates, of which 4 (Rv1572-1576c, Rv1585c-1587c, MT1798-Rv1755c and Rv1761c) were variably deleted among ST42 isolates, indicating a closer relationship between the Beijing and ST42 lineages. The TbD1 region, Mb1582-Mb1583 was deleted in Beijing and ST42 isolates. One M.bovis gene of unknown function, Mb3184c was present in all isolates, except 11 of 13 ST42 isolates. The CDC1551 gene, MT1360 coding for a putative adenylate cyclase, was present in all Beijing and ST42 isolates (except 1). The pks15/1 gene, coding for a putative virulence factor, was intact in all Beijing and non-Beijing isolates, except in ST42 and ST53 isolates. Conclusion. This study describes previously unreported deletions/extra regions in Beijing and non-Beijing M.tuberculosis isolates. The modern and highly frequent ST42 lineage showed a closer relationship to the hypervirulent Beijing lineage than to the ancient non-Beijing lineages. The pks15/1 gene was disrupted only in modern non-Beijing isolates. This is the first report of an in-depth analysis on the genomic diversity of M.tuberculosis isolates from Myanmar. Data is also available from http://bugs.sgul.ac.uk/E-BUGS-66

Project description:BackgroundThe most prevalent strains of Mycobacterium tuberculosis (M.tb) in Beijing belong to the Beijing genotype family. The influence of Beijing genotype prevalence on the development of drug resistance, and the association of infection with Beijing genotype M.tb with population characteristics, in Beijing, however, are still unclear.MethodsIn this retrospective study, 1189 isolates were subjected to drug susceptibility testing (DST) and molecular epidemiological analysis, and differences in the percentage of drug resistance between Beijing and non-Beijing genotype strains were compared. The association between the occurrence of drug resistance and the prevalence of Beijing genotype M.tb was analyzed using statistical methods.ResultsThe Beijing genotype family was the dominant genotype (83.3%) among the 1189 M.tb isolates. Beijing genotype M.tb strains were more likely to spread among males [p = 0.018, OR (95% CI):1.127(1.004-1.264)] and people in the 45-64 age group [p = 0.016, OR (95% CI): 1.438 (1.027-2.015)]. On the contrary, non-Beijing genotype M.tb strains were more probably disseminated among the over 65 [p = 0.005, OR (95% CI):0.653 (0.474-0.9)] and non-resident population [p = 0.035, OR (95% CI):1.185(0.985-1.427)]. DST results showed that 849 (71.4%) strains were fully sensitive to first-line drugs, while 340 (28.6%) strains were resistant to at least one drug, and 9% (107/1189) were MDR-TB. The frequency of INH-resistance among Beijing genotype strains was significantly lower than that among non-Beijing genotype strains (p = 0.032). In addition, the Beijing genotype family readily formed clusters.ConclusionsOur findings indicate that male and middle-aged people were more probably be infected by Beijing genotype M.tb, older people and non-residents were more probably be infected by non-Beijing genotype M.tb. The high percentage of resistance to INH occurring in non-Beijing genotype strains suggested that non-Beijing genotype strains should be given much more interest in Beijing.

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