Mutations associated with in vitro resistance to bedaquiline in Mycobacterium tuberculosis isolates in Australia

Elena Martinez; Daneeta Hennessy; Peter Jelfs; Taryn Crighton; Sharon C-A Chen; Vitali Sintchenko

doi:10.1016/j.tube.2018.04.007

Mutations associated with in vitro resistance to bedaquiline in Mycobacterium tuberculosis isolates in Australia

Tuberculosis (Edinb). 2018 Jul:111:31-34. doi: 10.1016/j.tube.2018.04.007. Epub 2018 Apr 25.

Authors

Elena Martinez¹, Daneeta Hennessy², Peter Jelfs³, Taryn Crighton⁴, Sharon C-A Chen⁵, Vitali Sintchenko⁵

Affiliations

¹ Centre for Infectious Diseases and Microbiology- Public Health, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia; Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, New South Wales, Australia; NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology - Western, Sydney, New South Wales, Australia. Electronic address: maria.martinezdiaz@sydney.edu.au.
² Centre for Infectious Diseases and Microbiology- Public Health, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia.
³ Centre for Infectious Diseases and Microbiology- Public Health, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia; NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology - Western, Sydney, New South Wales, Australia.
⁴ NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology - Western, Sydney, New South Wales, Australia.
⁵ Centre for Infectious Diseases and Microbiology- Public Health, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia; Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, New South Wales, Australia; NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology - Western, Sydney, New South Wales, Australia.

PMID: 30029911
DOI: 10.1016/j.tube.2018.04.007

Abstract

Genome-wide analysis of 517 Mycobacterium tuberculosis isolates from New South Wales, Australia, have identified previously reported and 8 new mutations in Rv0678 and atpE genes linked to in vitro resistance to bedaquiline, a new class of antimycobacterial drugs. These mutations were present in 2.9% of prospectively sequenced genomes but in 10.6% of strains that were phenotypically multidrug-resistant. However only 14% of isolates with these mutations demonstrated elevated minimum inhibitory concentrations to bedaquiline.

Keywords: Bedaquiline resistance; Multidrug-resistant tuberculosis; Mycobacterium tuberculosis; Whole genome sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antitubercular Agents / pharmacology*
DNA Mutational Analysis
DNA, Bacterial / genetics*
Diarylquinolines / pharmacology*
Drug Resistance, Multiple, Bacterial / genetics*
Genome, Bacterial
Genome-Wide Association Study
Genotype
Humans
Microbial Sensitivity Tests
Mutation*
Mycobacterium tuberculosis / drug effects*
Mycobacterium tuberculosis / genetics*
Mycobacterium tuberculosis / pathogenicity
New South Wales
Phenotype
Tuberculosis, Multidrug-Resistant / diagnosis
Tuberculosis, Multidrug-Resistant / drug therapy*
Tuberculosis, Multidrug-Resistant / microbiology*

Substances

Antitubercular Agents
DNA, Bacterial
Diarylquinolines
bedaquiline