The potassium transporter KdpA affects persister formation by regulating ATP levels in Mycobacterium marinum
Mycobacterial persistence mechanisms remain to be fully characterized. Screening a transposon insertion library of Mycobacterium marinum identified kdpA, whose inactivation reduced the fraction of persisters after exposure to rifampicin. kdpA encodes a transmembrane protein that is part of the Kdp-A...
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Taylor & Francis Group
2020-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2019.1710090 |
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| author | Xiaofan Liu Chuan Wang Bo Yan Liangdong Lyu Howard E. Takiff Qian Gao |
| author_facet | Xiaofan Liu Chuan Wang Bo Yan Liangdong Lyu Howard E. Takiff Qian Gao |
| author_sort | Xiaofan Liu |
| collection | DOAJ |
| description | Mycobacterial persistence mechanisms remain to be fully characterized. Screening a transposon insertion library of Mycobacterium marinum identified kdpA, whose inactivation reduced the fraction of persisters after exposure to rifampicin. kdpA encodes a transmembrane protein that is part of the Kdp-ATPase, an ATP-dependent high-affinity potassium (K+) transport system. We found that kdpA is induced under low K+ conditions and is required for pH homeostasis and growth in media with low concentrations of K+. The inactivation of the Kdp system in a kdpA insertion mutant caused hyperpolarization of the cross-membrane potential, increased proton motive force (PMF) and elevated levels of intracellular ATP. The KdpA mutant phenotype could be complemented with a functional kdpA gene or supplementation with high K+ concentrations. Taken together, our results suggest that the Kdp system is required for ATP homeostasis and persister formation. The results also confirm that ATP-mediated regulation of persister formation is a general mechanism in bacteria, and suggest that K+ transporters could play a role in the regulation of ATP levels and persistence. These findings could have implications for the development of new drugs that could either target persisters or reduce their presence. |
| format | Article |
| id | doaj-art-2ec6ea5b634942f1a047f3a588a2e6f4 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
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| series | Emerging Microbes and Infections |
| spelling | doaj-art-2ec6ea5b634942f1a047f3a588a2e6f42025-08-20T02:12:20ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-019112913910.1080/22221751.2019.1710090The potassium transporter KdpA affects persister formation by regulating ATP levels in Mycobacterium marinumXiaofan Liu0Chuan Wang1Bo Yan2Liangdong Lyu3Howard E. Takiff4Qian Gao5Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of ChinaKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of ChinaKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of ChinaIntegrated Mycobacterial Pathogenomics Unit, Institut Pasteur, Paris, FranceKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of ChinaMycobacterial persistence mechanisms remain to be fully characterized. Screening a transposon insertion library of Mycobacterium marinum identified kdpA, whose inactivation reduced the fraction of persisters after exposure to rifampicin. kdpA encodes a transmembrane protein that is part of the Kdp-ATPase, an ATP-dependent high-affinity potassium (K+) transport system. We found that kdpA is induced under low K+ conditions and is required for pH homeostasis and growth in media with low concentrations of K+. The inactivation of the Kdp system in a kdpA insertion mutant caused hyperpolarization of the cross-membrane potential, increased proton motive force (PMF) and elevated levels of intracellular ATP. The KdpA mutant phenotype could be complemented with a functional kdpA gene or supplementation with high K+ concentrations. Taken together, our results suggest that the Kdp system is required for ATP homeostasis and persister formation. The results also confirm that ATP-mediated regulation of persister formation is a general mechanism in bacteria, and suggest that K+ transporters could play a role in the regulation of ATP levels and persistence. These findings could have implications for the development of new drugs that could either target persisters or reduce their presence.https://www.tandfonline.com/doi/10.1080/22221751.2019.1710090PersisterMycobacterium marinumpotassiumATPrifampicin |
| spellingShingle | Xiaofan Liu Chuan Wang Bo Yan Liangdong Lyu Howard E. Takiff Qian Gao The potassium transporter KdpA affects persister formation by regulating ATP levels in Mycobacterium marinum Emerging Microbes and Infections Persister Mycobacterium marinum potassium ATP rifampicin |
| title | The potassium transporter KdpA affects persister formation by regulating ATP levels in Mycobacterium marinum |
| title_full | The potassium transporter KdpA affects persister formation by regulating ATP levels in Mycobacterium marinum |
| title_fullStr | The potassium transporter KdpA affects persister formation by regulating ATP levels in Mycobacterium marinum |
| title_full_unstemmed | The potassium transporter KdpA affects persister formation by regulating ATP levels in Mycobacterium marinum |
| title_short | The potassium transporter KdpA affects persister formation by regulating ATP levels in Mycobacterium marinum |
| title_sort | potassium transporter kdpa affects persister formation by regulating atp levels in mycobacterium marinum |
| topic | Persister Mycobacterium marinum potassium ATP rifampicin |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2019.1710090 |
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