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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author 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.,
Project Forschungspauschale Forschungsratspräsident SNF
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Original article (peer-reviewed)

Journal Antimicrobial Agents and Chemotherapy
Volume (Issue) 64(11)
Page(s) e00513-20
Title of proceedings Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.00513-20

Open Access

URL http://doi.org/10.1128/AAC.00513-20
Type of Open Access Green OA Embargo (Freely available via Repository after an embargo)

Abstract

ABSTRACT Mutations in the genes of the F 420 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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