Natural Polymorphisms in Mycobacterium tuberculosis Conferring Resistance to Delamanid in Drug-Naive Patients.
Martina L ReichmuthRico HömkeKathrin ZürcherPeter SanderAnchalee AvihingsanonJimena CollantesChloé LoiseauSonia BorrellMiriam ReinhardRobert J WilkinsonMarcel YotebiengLukas FennerErik C BöttgerSebastien GagneuxMatthias EggerPeter M KellerPublished in: Antimicrobial agents and chemotherapy (2020)
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.
Keyphrases
- mycobacterium tuberculosis
- escherichia coli
- signaling pathway
- pulmonary tuberculosis
- end stage renal disease
- genome wide
- newly diagnosed
- hiv infected
- chronic kidney disease
- epithelial mesenchymal transition
- prognostic factors
- case report
- peritoneal dialysis
- emergency department
- pi k akt
- adverse drug
- patient reported outcomes
- gene expression
- cell proliferation