RNase HI Depletion Strongly Potentiates Cell Killing by Rifampicin in Mycobacteria

Author:

Al-Zubaidi Abeer12,Cheung Chen-Yi3,Cook Gregory M.23ORCID,Taiaroa George4,Mizrahi Valerie5678,Lott J. Shaun12ORCID,Dawes Stephanie S.12

Affiliation:

1. School of Biological Sciences, The University of Auckland, Auckland, New Zealand

2. Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand

3. Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand

4. Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia

5. South African Medical Research Council, National Health Laboratory Service, University of Cape Town Molecular Mycobacteriology Research Unit, University of Cape Town, Cape Town, South Africa

6. Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical TB Research, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

7. Department of Pathology, University of Cape Town, Cape Town, South Africa

8. Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa

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.

Funder

Manatu Hauora | Health Research Council of New Zealand

Maurice Wilkins Centre for Molecular Biodiscovery

National Research Foundation

South African Medical Research Council

South African National Health Laboratory Serivce Research Trust

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference99 articles.

1. O’Neill J. 2016. Tackling drug-resistant infections globally: final report and recommendations. Wellcome Trust, London, UK.

2. World Health Organisation. 2020. Consolidated guidelines on tuberculosis. https://www.who.int/publications/i/item/9789240007048.

3. Treatment of Highly Drug-Resistant Pulmonary Tuberculosis

4. Hybridization of RNA to double-stranded DNA: formation of R-loops.

5. Overexpression of RNase H partially complements the growth defect of an Escherichia coli delta topA mutant: R-loop formation is a major problem in the absence of DNA topoisomerase I.

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