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Natural Polymorphisms in Mycobacterium tuberculosis Conferring Resistance to Delamanid in Drug-naïve Patients


Reichmuth, Martina L; Hömke, Rico; Zürcher, Kathrin; Sander, Peter; Avihingsanon, Anchalee; Collantes, Jimena; Loiseau, Chloé; Borrell, Sonia; Reinhard, Miriam; Wilkinson, Robert J; Yotebieng, Marcel; Fenner, Lukas; Böttger, Erik C; Gagneux, Sebastien; Egger, Matthias; Keller, Peter M (2020). Natural Polymorphisms in Mycobacterium tuberculosis Conferring Resistance to Delamanid in Drug-naïve Patients. Antimicrobial Agents and Chemotherapy, 64(11):e00513-20.

Abstract

Mutations in the genes of the F420 signaling pathway of Mycobacterium tuberculosis complex, including dnn, fgd1, fbiA, fbiB, fbiC, and fbiD, can lead to delamanid resistance. We searched for such mutations among 129 M. tuberculosis strains from Asia, South America, and Africa using whole-genome sequencing; 70 (54%) strains had at least one mutation in one of the genes. For 10 strains with mutations, we determined the MIC of delamanid. We found one strain from a delamanid-naive patient carrying the natural polymorphism Tyr29del (ddn) that was associated with a critical delamanid MIC.

Abstract

Mutations in the genes of the F420 signaling pathway of Mycobacterium tuberculosis complex, including dnn, fgd1, fbiA, fbiB, fbiC, and fbiD, can lead to delamanid resistance. We searched for such mutations among 129 M. tuberculosis strains from Asia, South America, and Africa using whole-genome sequencing; 70 (54%) strains had at least one mutation in one of the genes. For 10 strains with mutations, we determined the MIC of delamanid. We found one strain from a delamanid-naive patient carrying the natural polymorphism Tyr29del (ddn) that was associated with a critical delamanid MIC.

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Additional indexing

Contributors:International epidemiologyDatabases to Evaluate AIDS (IeDEA)
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Pharmacology
Health Sciences > Pharmacology (medical)
Health Sciences > Infectious Diseases
Language:English
Date:31 August 2020
Deposited On:19 Jan 2021 12:42
Last Modified:24 Sep 2023 01:43
Publisher:American Society for Microbiology
ISSN:0066-4804
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1128/AAC.00513-20
PubMed ID:32868333
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)