Journal article
RNase HI Depletion Strongly Potentiates Cell Killing by Rifampicin in Mycobacteria
A Al-Zubaidi, CY Cheung, GM Cook, G Taiaroa, V Mizrahi, JS Lott, SS Dawes
Antimicrobial Agents and Chemotherapy | AMER SOC MICROBIOLOGY | Published : 2022
DOI: 10.1128/aac.02091-21
Abstract
Multidrug-resistant (MDR) tuberculosis (TB) is defined by the resistance of Mycobacterium tuberculosis, the causative organism, to the first-line antibiotics rifampicin and isoniazid. Mitigating or reversing resistance to these drugs offers a means of preserving and extending their use in TB treatment. R-loops are RNA/DNA hybrids that are formed in the genome during transcription, and they can be lethal to the cell if not resolved. RNase HI is an enzyme that removes R-loops, and this activity is essential in M. tuberculosis: knockouts of rnhC, the gene encoding RNase HI, are nonviable. This essentiality makes it a candidate target for the development of new antibiotics. In the model organism..
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Awarded by South African Medical Research Council
Funding Acknowledgements
We thank the Health Research Council of New Zealand (grant 20/798 to S.S.D.), the Maurice Wilkins Centre for Molecular Biodiscovery (awards to S.S.D. and J.S.L.), the South African National Research Foundation (award to S.S.D.), the South African National Laboratory Service Research Trust (award to S.S.D.), and the South African Medical Research Council (award to V.M.) for financial support.