Predicting nitroimidazole antibiotic resistance mutations in Mycobacterium tuberculosis with protein engineering.

ABSTRACT: Our inability to predict which mutations could result in antibiotic resistance has made it difficult to rapidly identify the emergence of resistance, identify pre-existing resistant populations, and manage our use of antibiotics to effectively treat patients and prevent or slow the spread of resistance. Here we investigated the potential for resistance against the new antitubercular nitroimidazole prodrugs pretomanid and delamanid to emerge in Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). Deazaflavin-dependent nitroreductase (Ddn) is the only identified enzyme within M. tuberculosis that activates these prodrugs, via an F420H2-dependent reaction. We show that the native menaquinone-reductase activity of Ddn is essential for emergence from hypoxia, which suggests tha

SUBMITTER: Lee BM 

PROVIDER: S-EPMC7032734 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature