M. tuberculosis relies on trace oxygen to maintain energy homeostasis and survive in hypoxic environments
Summary: The bioenergetic mechanisms by which Mycobacterium tuberculosis survives hypoxia are poorly understood. Current models assume that the bacterium shifts to an alternate electron acceptor or fermentation to maintain membrane potential and ATP synthesis. Counterintuitively, we find here that o...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723004552 |
| _version_ | 1827958105770557440 |
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| author | Nitin Pal Kalia Samsher Singh Kiel Hards Chen-Yi Cheung Ekaterina Sviriaeva Amir Banaei-Esfahani Ruedi Aebersold Michael Berney Gregory M. Cook Kevin Pethe |
| author_facet | Nitin Pal Kalia Samsher Singh Kiel Hards Chen-Yi Cheung Ekaterina Sviriaeva Amir Banaei-Esfahani Ruedi Aebersold Michael Berney Gregory M. Cook Kevin Pethe |
| author_sort | Nitin Pal Kalia |
| collection | DOAJ |
| description | Summary: The bioenergetic mechanisms by which Mycobacterium tuberculosis survives hypoxia are poorly understood. Current models assume that the bacterium shifts to an alternate electron acceptor or fermentation to maintain membrane potential and ATP synthesis. Counterintuitively, we find here that oxygen itself is the principal terminal electron acceptor during hypoxic dormancy. M. tuberculosis can metabolize oxygen efficiently at least two orders of magnitude below the concentration predicted to occur in hypoxic lung granulomas. Despite a difference in apparent affinity for oxygen, both the cytochrome bcc:aa3 and cytochrome bd oxidase respiratory branches are required for hypoxic respiration. Simultaneous inhibition of both oxidases blocks oxygen consumption, reduces ATP levels, and kills M. tuberculosis under hypoxia. The capacity of mycobacteria to scavenge trace levels of oxygen, coupled with the absence of complex regulatory mechanisms to achieve hierarchal control of the terminal oxidases, may be a key determinant of long-term M. tuberculosis survival in hypoxic lung granulomas. |
| first_indexed | 2024-04-09T15:30:21Z |
| format | Article |
| id | doaj.art-9d80392a417e4e81ac7c55890f889fb7 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-09T15:30:21Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-9d80392a417e4e81ac7c55890f889fb72023-04-28T08:55:24ZengElsevierCell Reports2211-12472023-05-01425112444M. tuberculosis relies on trace oxygen to maintain energy homeostasis and survive in hypoxic environmentsNitin Pal Kalia0Samsher Singh1Kiel Hards2Chen-Yi Cheung3Ekaterina Sviriaeva4Amir Banaei-Esfahani5Ruedi Aebersold6Michael Berney7Gregory M. Cook8Kevin Pethe9Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore; Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER-H) Hyderabad, Hyderabad, Telangana 500037, IndiaLee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, SingaporeDepartment of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 92019, New ZealandDepartment of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin 9054, New ZealandLee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, SingaporeDepartment of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8057 Zurich, SwitzerlandDepartment of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8057 Zurich, Switzerland; Faculty of Science, University of Zurich, 8057 Zurich, SwitzerlandDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 92019, New Zealand; Corresponding authorLee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore; Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551, Singapore; National Centre for Infectious Diseases, Singapore 308442, Singapore; Corresponding authorSummary: The bioenergetic mechanisms by which Mycobacterium tuberculosis survives hypoxia are poorly understood. Current models assume that the bacterium shifts to an alternate electron acceptor or fermentation to maintain membrane potential and ATP synthesis. Counterintuitively, we find here that oxygen itself is the principal terminal electron acceptor during hypoxic dormancy. M. tuberculosis can metabolize oxygen efficiently at least two orders of magnitude below the concentration predicted to occur in hypoxic lung granulomas. Despite a difference in apparent affinity for oxygen, both the cytochrome bcc:aa3 and cytochrome bd oxidase respiratory branches are required for hypoxic respiration. Simultaneous inhibition of both oxidases blocks oxygen consumption, reduces ATP levels, and kills M. tuberculosis under hypoxia. The capacity of mycobacteria to scavenge trace levels of oxygen, coupled with the absence of complex regulatory mechanisms to achieve hierarchal control of the terminal oxidases, may be a key determinant of long-term M. tuberculosis survival in hypoxic lung granulomas.http://www.sciencedirect.com/science/article/pii/S2211124723004552CP: Microbiology |
| spellingShingle | Nitin Pal Kalia Samsher Singh Kiel Hards Chen-Yi Cheung Ekaterina Sviriaeva Amir Banaei-Esfahani Ruedi Aebersold Michael Berney Gregory M. Cook Kevin Pethe M. tuberculosis relies on trace oxygen to maintain energy homeostasis and survive in hypoxic environments Cell Reports CP: Microbiology |
| title | M. tuberculosis relies on trace oxygen to maintain energy homeostasis and survive in hypoxic environments |
| title_full | M. tuberculosis relies on trace oxygen to maintain energy homeostasis and survive in hypoxic environments |
| title_fullStr | M. tuberculosis relies on trace oxygen to maintain energy homeostasis and survive in hypoxic environments |
| title_full_unstemmed | M. tuberculosis relies on trace oxygen to maintain energy homeostasis and survive in hypoxic environments |
| title_short | M. tuberculosis relies on trace oxygen to maintain energy homeostasis and survive in hypoxic environments |
| title_sort | m tuberculosis relies on trace oxygen to maintain energy homeostasis and survive in hypoxic environments |
| topic | CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723004552 |
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