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

By Martina Reichmuth, Rico Hoemke, Kathrin Zürcher, Peter Sander, Anchalee Avihingsanon, Jimena Collantes, Chloé Loiseau, Sonia Borrell, Miriam Reinhard, Robert J. Wilkinson, Marcel Yotebieng, Lukas Fenner, Erik C. Böttger, Sebastien Gagneux, Matthias Egger, Peter M. Keller

Posted 11 Aug 2020
medRxiv DOI: 10.1101/2020.08.07.20167130

Mutations in the genes of the F420 signaling pathway, including dnn, fgd1, fbiA, fbiB, fbiC, and fbiD, of Mycobacterium tuberculosis (Mtb) complex can lead to delamanid resistance. We searched for such mutations among 129 Mtb 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 ten strains with mutations, we determined the minimum inhibitory concentration (MIC) of delamanid. We found one strain from a delamanid-naive patient carrying the natural polymorphism Tyr29del (ddn) that was associated with a critical MIC to delamanid.

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