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

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.

SUBMITTER: Reichmuth ML

PROVIDER: S-EPMC7577131 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Reichmuth Martina L ML Hömke Rico R Zürcher Kathrin K Sander Peter P Avihingsanon Anchalee A Collantes Jimena J Loiseau Chloé C Borrell Sonia S Reinhard Miriam M Wilkinson Robert J RJ Yotebieng Marcel M Fenner Lukas L Böttger Erik C EC Gagneux Sebastien S Egger Matthias M Keller Peter M PM

Antimicrobial agents and chemotherapy 20201020 11

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 delam ...[more]

PMID: 32868333

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