TY - JOUR
T1 - Natural Polymorphisms in Mycobacterium tuberculosis Conferring Resistance to Delamanid in Drug-Naive Patients
AU - International epidemiology Databases to Evaluate AIDS (IeDEA)
AU - Reichmuth, Martina L.
AU - Hömke, Rico
AU - Zürcher, Kathrin
AU - Sander, Peter
AU - Avihingsanon, Anchalee
AU - Collantes, Jimena
AU - Loiseau, Chloé
AU - Borrell, Sonia
AU - Reinhard, Miriam
AU - Wilkinson, Robert J.
AU - Yotebieng, Marcel
AU - Fenner, Lukas
AU - Böttger, Erik C.
AU - Gagneux, Sebastien
AU - Egger, Matthias
AU - Keller, Peter M.
N1 - Publisher Copyright:
Copyright © 2020 Reichmuth et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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.
KW - Delamanid
KW - Drug resistance
KW - Mutations
KW - Mycobacterium tuberculosis
KW - Natural polymorphism
KW - Resistance
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U2 - 10.1128/AAC.00513-20
DO - 10.1128/AAC.00513-20
M3 - Article
C2 - 32868333
AN - SCOPUS:85094221055
SN - 0066-4804
VL - 64
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 11
M1 - e00513
ER -
