Variants in Bedaquiline-Candidate-Resistance Genes: Prevalence in Bedaquiline-Naive Patients, Effect on MIC, and Association with Mycobacterium tuberculosis Lineage.

antibiotic resistance antimicrobial resistance bedaquiline drug-resistant tuberculosis epidemiology phenotypic drug susceptibility testing phylogeny tuberculosis whole-genome sequencing

Journal

Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061

Informations de publication

Date de publication:
19 07 2022
Historique:
pubmed: 28 6 2022
medline: 22 7 2022
entrez: 27 6 2022
Statut: ppublish

Résumé

Studies have shown that variants in bedaquiline-resistance genes can occur in isolates from bedaquiline-naive patients. We assessed the prevalence of variants in all bedaquiline-candidate-resistance genes in bedaquiline-naive patients, investigated the association between these variants and lineage, and the effect on phenotype. We used whole-genome sequencing to identify variants in bedaquiline-resistance genes in isolates from 509 bedaquiline treatment naive South African tuberculosis patients. A phylogenetic tree was constructed to investigate the association with the isolate lineage background. Bedaquiline MIC was determined using the UKMYC6 microtiter assay. Variants were identified in 502 of 509 isolates (98.6%), with the highest (85%) prevalence of variants in the

Identifiants

pubmed: 35758754
doi: 10.1128/aac.00322-22
pmc: PMC9295546
doi:

Substances chimiques

Antitubercular Agents 0
Diarylquinolines 0
bedaquiline 78846I289Y

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0032222

Subventions

Organisme : NIAID NIH HHS
ID : R21 AI135756
Pays : United States

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Auteurs

Emmanuel Rivière (E)

Tuberculosis Omics Research Consortium, Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerpgrid.5284.b, Antwerp, Belgium.
Adrem Data Lab, Department of Computer Science, Faculty of Sciences, University of Antwerpgrid.5284.b, Antwerp, Belgium.

Lennert Verboven (L)

Tuberculosis Omics Research Consortium, Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerpgrid.5284.b, Antwerp, Belgium.
Adrem Data Lab, Department of Computer Science, Faculty of Sciences, University of Antwerpgrid.5284.b, Antwerp, Belgium.

Anzaan Dippenaar (A)

Tuberculosis Omics Research Consortium, Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerpgrid.5284.b, Antwerp, Belgium.

Sander Goossens (S)

Tuberculosis Omics Research Consortium, Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerpgrid.5284.b, Antwerp, Belgium.
Adrem Data Lab, Department of Computer Science, Faculty of Sciences, University of Antwerpgrid.5284.b, Antwerp, Belgium.

Elise De Vos (E)

Tuberculosis Omics Research Consortium, Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerpgrid.5284.b, Antwerp, Belgium.

Elizabeth Streicher (E)

Division of Molecular Biology and Human Genetics, South African Medical Research Council Centre for Tuberculosis Research, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch Universitygrid.11956.3a, Cape Town, South Africa.

Bart Cuypers (B)

Adrem Data Lab, Department of Computer Science, Faculty of Sciences, University of Antwerpgrid.5284.b, Antwerp, Belgium.
Molecular Parasitology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Kris Laukens (K)

Adrem Data Lab, Department of Computer Science, Faculty of Sciences, University of Antwerpgrid.5284.b, Antwerp, Belgium.

Fathia Ben-Rached (F)

Computational Bioscience Research Centre, Biological Environmental Sciences and Engineering Division, King Abdullah University of Science and Technologygrid.45672.32, Thuwal, Saudi Arabia.

Timothy C Rodwell (TC)

FIND, Geneva, Switzerland.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, La Jolla, California, USA.

Arnab Pain (A)

Computational Bioscience Research Centre, Biological Environmental Sciences and Engineering Division, King Abdullah University of Science and Technologygrid.45672.32, Thuwal, Saudi Arabia.
International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, Japan.

Robin M Warren (RM)

Division of Molecular Biology and Human Genetics, South African Medical Research Council Centre for Tuberculosis Research, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch Universitygrid.11956.3a, Cape Town, South Africa.

Tim H Heupink (TH)

Tuberculosis Omics Research Consortium, Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerpgrid.5284.b, Antwerp, Belgium.

Annelies Van Rie (A)

Tuberculosis Omics Research Consortium, Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of Antwerpgrid.5284.b, Antwerp, Belgium.

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Classifications MeSH