Dataset Information

Whole-Genome Sequence of the Potentially Hypertransmissible Multidrug-Resistant Mycobacterium tuberculosis Beijing Strain OM-V02_005.

ABSTRACT: We report the draft genome sequence of Mycobacterium tuberculosis Beijing strain OM-V02_005, which exhibits possible hypertransmissible characteristics among the population of patients with multidrug-resistant tuberculosis in Osaka Prefecture, the largest urban area in western Japan.

SUBMITTER: Tateishi Y

PROVIDER: S-EPMC3738908 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Whole-Genome Sequence of the Potentially Hypertransmissible Multidrug-Resistant Mycobacterium tuberculosis Beijing Strain OM-V02_005.

Tateishi Yoshitaka Y Tamaru Aki A Ogura Yoshitoshi Y Niki Mamiko M Wada Takayuki T Yamamoto Taro T Hirata Kazuto K Hayashi Tetsuya T Matsumoto Sohkichi S

Genome announcements 20130808 4

We report the draft genome sequence of Mycobacterium tuberculosis Beijing strain OM-V02_005, which exhibits possible hypertransmissible characteristics among the population of patients with multidrug-resistant tuberculosis in Osaka Prefecture, the largest urban area in western Japan. ...[more]

PMID: 23929492

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Project description:Multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains represent a major threat for tuberculosis (TB) control. Treatment of MDR-TB patients is long and less effective, resulting in a significant number of treatment failures. The development of further resistances leads to extensively drug-resistant (XDR) variants. However, data on the individual reasons for treatment failure, e.g. an induced mutational burst, and on the evolution of bacteria in the patient are only sparsely available. To address this question, we investigated the intra-patient evolution of serial MTBC isolates obtained from three MDR-TB patients undergoing longitudinal treatment, finally leading to XDR-TB. Sequential isolates displayed identical IS6110 fingerprint patterns, suggesting the absence of exogenous re-infection. We utilized whole genome sequencing (WGS) to screen for variations in three isolates from Patient A and four isolates from Patient B and C, respectively. Acquired polymorphisms were subsequently validated in up to 15 serial isolates by Sanger sequencing. We determined eight (Patient A) and nine (Patient B) polymorphisms, which occurred in a stepwise manner during the course of the therapy and were linked to resistance or a potential compensatory mechanism. For both patients, our analysis revealed the long-term co-existence of clonal subpopulations that displayed different drug resistance allele combinations. Out of these, the most resistant clone was fixed in the population. In contrast, baseline and follow-up isolates of Patient C were distinguished each by eleven unique polymorphisms, indicating an exogenous re-infection with an XDR strain not detected by IS6110 RFLP typing. Our study demonstrates that intra-patient microevolution of MDR-MTBC strains under longitudinal treatment is more complex than previously anticipated. However, a mutator phenotype was not detected. The presence of different subpopulations might confound phenotypic and molecular drug resistance tests. Furthermore, high resolution WGS analysis is necessary to accurately detect exogenous re-infection as classical genotyping lacks discriminatory power in high incidence settings.

Dataset Information

Whole-Genome Sequence of the Potentially Hypertransmissible Multidrug-Resistant Mycobacterium tuberculosis Beijing Strain OM-V02_005.

Publications

Whole-Genome Sequence of the Potentially Hypertransmissible Multidrug-Resistant Mycobacterium tuberculosis Beijing Strain OM-V02_005.

Similar Datasets

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