Whole-genome sequencing reveals genetic signature of bedaquiline resistance in a clinical isolate of Mycobacterium tuberculosis

Kiran Chawla, Elena Martinez, Ajay Kumar, Vishnu Prasad Shenoy, Vitali Sintchenko

Research output: Contribution to journalComment/debate

Abstract

Objectives: The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains has opened up new challenges for tuberculosis (TB) control in India. This study examined molecular markers of resistance to bedaquiline, a new antituberculous drug with the potential to dramatically improve MDR-TB treatment outcomes and to reduce mortality. Methods: A clinical M. tuberculosis isolate with a MDR-TB profile was subjected to whole-genome sequencing using an Illumina NextSeq500 platform, followed by genome-wide sequence analysis. Results: A mutation in the Rv0678 coding region associated with in vitro bedaquiline resistance was identified. The strain represented the Delhi/CAS lineage. Conclusions: This first report of a potentially bedaquiline-resistant M. tuberculosis strain in India highlights the role of genome-wide sequence analysis of isolates from TB cases with a history of treatment in countries with a high burden of MDR-TB and XDR-TB.

Original languageEnglish
Pages (from-to)103-104
Number of pages2
JournalJournal of Global Antimicrobial Resistance
Volume15
DOIs
Publication statusPublished - 01-12-2018

Fingerprint

bedaquiline
Multidrug-Resistant Tuberculosis
Mycobacterium tuberculosis
Tuberculosis
Genome
Sequence Analysis
India
Pharmaceutical Preparations
Mutation
Mortality

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology and Allergy
  • Immunology
  • Microbiology (medical)

Cite this

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title = "Whole-genome sequencing reveals genetic signature of bedaquiline resistance in a clinical isolate of Mycobacterium tuberculosis",
abstract = "Objectives: The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains has opened up new challenges for tuberculosis (TB) control in India. This study examined molecular markers of resistance to bedaquiline, a new antituberculous drug with the potential to dramatically improve MDR-TB treatment outcomes and to reduce mortality. Methods: A clinical M. tuberculosis isolate with a MDR-TB profile was subjected to whole-genome sequencing using an Illumina NextSeq500 platform, followed by genome-wide sequence analysis. Results: A mutation in the Rv0678 coding region associated with in vitro bedaquiline resistance was identified. The strain represented the Delhi/CAS lineage. Conclusions: This first report of a potentially bedaquiline-resistant M. tuberculosis strain in India highlights the role of genome-wide sequence analysis of isolates from TB cases with a history of treatment in countries with a high burden of MDR-TB and XDR-TB.",
author = "Kiran Chawla and Elena Martinez and Ajay Kumar and Shenoy, {Vishnu Prasad} and Vitali Sintchenko",
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Whole-genome sequencing reveals genetic signature of bedaquiline resistance in a clinical isolate of Mycobacterium tuberculosis. / Chawla, Kiran; Martinez, Elena; Kumar, Ajay; Shenoy, Vishnu Prasad; Sintchenko, Vitali.

In: Journal of Global Antimicrobial Resistance, Vol. 15, 01.12.2018, p. 103-104.

Research output: Contribution to journalComment/debate

TY - JOUR

T1 - Whole-genome sequencing reveals genetic signature of bedaquiline resistance in a clinical isolate of Mycobacterium tuberculosis

AU - Chawla, Kiran

AU - Martinez, Elena

AU - Kumar, Ajay

AU - Shenoy, Vishnu Prasad

AU - Sintchenko, Vitali

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Objectives: The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains has opened up new challenges for tuberculosis (TB) control in India. This study examined molecular markers of resistance to bedaquiline, a new antituberculous drug with the potential to dramatically improve MDR-TB treatment outcomes and to reduce mortality. Methods: A clinical M. tuberculosis isolate with a MDR-TB profile was subjected to whole-genome sequencing using an Illumina NextSeq500 platform, followed by genome-wide sequence analysis. Results: A mutation in the Rv0678 coding region associated with in vitro bedaquiline resistance was identified. The strain represented the Delhi/CAS lineage. Conclusions: This first report of a potentially bedaquiline-resistant M. tuberculosis strain in India highlights the role of genome-wide sequence analysis of isolates from TB cases with a history of treatment in countries with a high burden of MDR-TB and XDR-TB.

AB - Objectives: The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains has opened up new challenges for tuberculosis (TB) control in India. This study examined molecular markers of resistance to bedaquiline, a new antituberculous drug with the potential to dramatically improve MDR-TB treatment outcomes and to reduce mortality. Methods: A clinical M. tuberculosis isolate with a MDR-TB profile was subjected to whole-genome sequencing using an Illumina NextSeq500 platform, followed by genome-wide sequence analysis. Results: A mutation in the Rv0678 coding region associated with in vitro bedaquiline resistance was identified. The strain represented the Delhi/CAS lineage. Conclusions: This first report of a potentially bedaquiline-resistant M. tuberculosis strain in India highlights the role of genome-wide sequence analysis of isolates from TB cases with a history of treatment in countries with a high burden of MDR-TB and XDR-TB.

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