Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP
ABSTRACT Bacterial persisters emerge and increase in numbers over time as a bacterial culture grows from log phase to stationary phase. However, the underlying basis of the inevitable tendency is unclear. In this study, we investigated the role of nutrients in starvation-mediated persister formation...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-02-01
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| Series: | mSphere |
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| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00862-19 |
| _version_ | 1819011797000126464 |
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| author | Tao Xu Xuyang Wang Lu Meng Mengqi Zhu Jing Wu Yuanyuan Xu Ying Zhang Wenhong Zhang |
| author_facet | Tao Xu Xuyang Wang Lu Meng Mengqi Zhu Jing Wu Yuanyuan Xu Ying Zhang Wenhong Zhang |
| author_sort | Tao Xu |
| collection | DOAJ |
| description | ABSTRACT Bacterial persisters emerge and increase in numbers over time as a bacterial culture grows from log phase to stationary phase. However, the underlying basis of the inevitable tendency is unclear. In this study, we investigated the role of nutrients in starvation-mediated persister formation of Staphylococcus aureus. By screening of nutrient components, we found that starvation-induced persister formation of log-phase cultures could be reversed by addition of magnesium (Mg2+) but not amino acids, nucleotides, or other salts. Further, deprivation of extracellular Mg2+ reduced cytoplasmic ATP, inducing persistence without affecting cytoplasmic Mg2+ or membrane potential. Finally, we showed that Mg2+ reduced expression of stationary cell marker genes, cap5A and arcA. These findings indicate a connection between Mg2+ levels and ATP, which represents metabolic status and mediates antibiotic persistence during growth. IMPORTANCE Various genes have been identified to be involved in bacterial persister formation regardless of the presence or absence of persister genes. Despite recent discoveries of the roles of ATP and membrane potential in persister formation, the key element that triggers change of ATP or membrane potential remains elusive. Our work demonstrates that Mg2+ instead of other ions or nutrient components is the key element for persistence by inducing a decrease of cytoplasmic ATP, which subsequently induces persister formation. In addition, we observed tight regulation of genes for Mg2+ transport in different growth phases in S. aureus. These findings indicate that despite being a key nutrient, Mg2+ also served as a key signal in persister formation during growth. |
| first_indexed | 2024-12-21T01:33:52Z |
| format | Article |
| id | doaj.art-410a3043acde49a09d4e30d0eef192f8 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-21T01:33:52Z |
| publishDate | 2020-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-410a3043acde49a09d4e30d0eef192f82022-12-21T19:20:17ZengAmerican Society for MicrobiologymSphere2379-50422020-02-015110.1128/mSphere.00862-19Magnesium Links Starvation-Mediated Antibiotic Persistence to ATPTao Xu0Xuyang Wang1Lu Meng2Mengqi Zhu3Jing Wu4Yuanyuan Xu5Ying Zhang6Wenhong Zhang7Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaKey Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USADepartment of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaABSTRACT Bacterial persisters emerge and increase in numbers over time as a bacterial culture grows from log phase to stationary phase. However, the underlying basis of the inevitable tendency is unclear. In this study, we investigated the role of nutrients in starvation-mediated persister formation of Staphylococcus aureus. By screening of nutrient components, we found that starvation-induced persister formation of log-phase cultures could be reversed by addition of magnesium (Mg2+) but not amino acids, nucleotides, or other salts. Further, deprivation of extracellular Mg2+ reduced cytoplasmic ATP, inducing persistence without affecting cytoplasmic Mg2+ or membrane potential. Finally, we showed that Mg2+ reduced expression of stationary cell marker genes, cap5A and arcA. These findings indicate a connection between Mg2+ levels and ATP, which represents metabolic status and mediates antibiotic persistence during growth. IMPORTANCE Various genes have been identified to be involved in bacterial persister formation regardless of the presence or absence of persister genes. Despite recent discoveries of the roles of ATP and membrane potential in persister formation, the key element that triggers change of ATP or membrane potential remains elusive. Our work demonstrates that Mg2+ instead of other ions or nutrient components is the key element for persistence by inducing a decrease of cytoplasmic ATP, which subsequently induces persister formation. In addition, we observed tight regulation of genes for Mg2+ transport in different growth phases in S. aureus. These findings indicate that despite being a key nutrient, Mg2+ also served as a key signal in persister formation during growth.https://journals.asm.org/doi/10.1128/mSphere.00862-19ATPStaphylococcus aureusantibiotic persistencemagnesium |
| spellingShingle | Tao Xu Xuyang Wang Lu Meng Mengqi Zhu Jing Wu Yuanyuan Xu Ying Zhang Wenhong Zhang Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP mSphere ATP Staphylococcus aureus antibiotic persistence magnesium |
| title | Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP |
| title_full | Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP |
| title_fullStr | Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP |
| title_full_unstemmed | Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP |
| title_short | Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP |
| title_sort | magnesium links starvation mediated antibiotic persistence to atp |
| topic | ATP Staphylococcus aureus antibiotic persistence magnesium |
| url | https://journals.asm.org/doi/10.1128/mSphere.00862-19 |
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