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. 2020 Oct 20;64(11):e00513-20.
doi: 10.1128/AAC.00513-20. Print 2020 Oct 20.

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

Martina L Reichmuth #  1 , Rico Hömke #  2   3 , Kathrin Zürcher  1 , Peter Sander  2   3 , Anchalee Avihingsanon  4 , Jimena Collantes  5 , Chloé Loiseau  6   7 , Sonia Borrell  6   7 , Miriam Reinhard  6   7 , Robert J Wilkinson  8   9   10 , Marcel Yotebieng  11   12 , Lukas Fenner  1 , Erik C Böttger  2   3 , Sebastien Gagneux  6   7 , Matthias Egger  1   13 , Peter M Keller  14   3   15
Affiliations

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

Martina L Reichmuth et al. Antimicrob Agents Chemother. .

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.

Keywords: Mycobacterium tuberculosis; delamanid; drug resistance; mutations; natural polymorphism; resistance.

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