Peer-Reviewed Publication
Nat Commun2024;15(1):9792.November 13, 2024Journal Article
Catalase activity deficiency sensitizes multidrug-resistant Mycobacterium tuberculosis to the ATP synthase inhibitor bedaquiline.
Boatema Ofori-Anyinam1,2, Meagan Hamblin3,4, Miranda L Coldren5, Barry Li1,2, Gautam Mereddy1,2, Mustafa Shaikh1,2, Avi Shah1,2, Courtney Grady1,6, Navpreet Ranu3,7,8, Sean Lu1,2, Paul C Blainey3,7,9, Shuyi Ma5,10,11,12, James J Collins3,7,13, Jason H Yang14,15
1Ruy V. Lourenço Center for Emerging and Re-Emerging Pathogens, Rutgers New Jersey Medical School, Newark, NJ, 07103, USA.
2Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, 07103, USA.
3Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
4Eversana Consulting, Boston, MA, 02120, USA.
5Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, 98105, USA.
6Public Health Research Institute, Rutgers New Jersey Medical School, Newark, NJ, 07103, USA.
7Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
8insitro, South San Francisco, CA, 94080, USA.
9Koch Institute of Integrative Cancer Research at MIT, Cambridge, MA, 02139, USA.
10Department of Pediatrics, University of Washington, Seattle, WA, 98195, USA.
11Department of Chemical Engineering, University of Washington, Seattle, WA, 98195, USA.
12Pathobiology Graduate Program, Department of Global Health, University of Washington, Seattle, WA, 98195, USA.
13Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
14Ruy V. Lourenço Center for Emerging and Re-Emerging Pathogens, Rutgers New Jersey Medical School, Newark, NJ, 07103, USA. jason.y@rutgers.edu.
15Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, 07103, USA. jason.y@rutgers.edu.
Abstract
Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to the first-line drugs isoniazid and rifampin, is a growing source of global mortality and threatens global control of tuberculosis disease. The diarylquinoline bedaquiline has recently emerged as a highly efficacious drug against MDR-TB and kills Mycobacterium tuberculosis by inhibiting mycobacterial ATP synthase. However, the mech…
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