Conference Proceedings
Predicting nitroimidazole antibiotic resistance mutations in Mycobacterium tuberculosis with protein engineering
Brendon Lee, Deepak Almeida, Livnat Afriat-Jurnou, Htin Aung, Brian Forde, Liam Harold, Kiel Hards, Sacha Pidot, Hafna Ahmed, Elaaf Mohamed, Mathew Taylor, Nicholas West, Timothy Stinear, Chris Greening, Scott Beatson, Gregory Cook, Eric Nuermberger, Colin Jackson
FASEB JOURNAL | WILEY | Published : 2020
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 ..
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Awarded by NHMRC
Awarded by ARC DECRA Fellowship
Awarded by U.S. National Institutes of Health
Funding Acknowledgements
This work was supported by by NHMRC Project Grant APP1128929 (to C. J. J., C. G., and G. M. C.). In addition, this work was supported by an ARC DECRA Fellowship DE170100310, and NHMRC New Investigator Grant APP1139832 (to C. G.). SAB is supported by an NHMRC Career Development Fellowship GNT1090456 (to SAB). DVA and ELN acknowledge the support of the U.S. National Institutes of Health (R01-AI111992).