Hypoionic Shock Facilitates Aminoglycoside Killing of Both Nutrient Shift- and Starvation-Induced Bacterial Persister Cells by Rapidly Enhancing Aminoglycoside Uptake
Bacterial persister cells are phenotypic variants that exhibit transient antibiotic tolerance and play a leading role in chronic infections and the development of antibiotic resistance. Determining the mechanism that underlies persister formation and developing anti-persister strategies, therefore,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.02028/full |
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| author | Zhongyu Chen Yuanyuan Gao Yuanyuan Gao Boyan Lv Fengqi Sun Wei Yao Yan Wang Xinmiao Fu Xinmiao Fu |
| author_facet | Zhongyu Chen Yuanyuan Gao Yuanyuan Gao Boyan Lv Fengqi Sun Wei Yao Yan Wang Xinmiao Fu Xinmiao Fu |
| author_sort | Zhongyu Chen |
| collection | DOAJ |
| description | Bacterial persister cells are phenotypic variants that exhibit transient antibiotic tolerance and play a leading role in chronic infections and the development of antibiotic resistance. Determining the mechanism that underlies persister formation and developing anti-persister strategies, therefore, are clinically important goals. Here, we report that many gram-negative and gram-positive bacteria become highly tolerant to typical bactericidal antibiotics when the carbon source for their antibiotic-sensitive exponential growth phase is shifted to fumarate, suggesting a role for fumarate in persister induction. Nutrient shift-induced Escherichia coli but not Staphylococcus aureus persister cells can be killed by aminoglycosides upon hypoionic shock (i.e., the absence of ions), which is achieved by suspending the persisters in aminoglycoside-containing pure water for only 1 or 2 min. Such potentiation can be abolished by inhibitors of the electron transport chain (e.g., NaN3) or proton motive force (e.g., CCCP). Additionally, we show that hypoionic shock facilitates the eradication of starvation-induced E. coli but not S. aureus persisters by aminoglycosides, and that such potentiation can be significantly suppressed by NaN3 or CCCP. Mechanistically, hypoionic shock dramatically enhances aminoglycoside uptake by both nutrient shift- and starvation-induced E. coli persisters, whereas CCCP can diminish this uptake. Results of our study illustrate the general role of fumarate in bacterial persistence and may open new avenues for persister eradication and aminoglycoside use. |
| first_indexed | 2024-12-22T03:46:30Z |
| format | Article |
| id | doaj.art-82695d215e1046b8837add7f8119149b |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T03:46:30Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-82695d215e1046b8837add7f8119149b2022-12-21T18:40:07ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-09-011010.3389/fmicb.2019.02028463582Hypoionic Shock Facilitates Aminoglycoside Killing of Both Nutrient Shift- and Starvation-Induced Bacterial Persister Cells by Rapidly Enhancing Aminoglycoside UptakeZhongyu Chen0Yuanyuan Gao1Yuanyuan Gao2Boyan Lv3Fengqi Sun4Wei Yao5Yan Wang6Xinmiao Fu7Xinmiao Fu8Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, ChinaProvincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, ChinaEngineering Research Center of Industrial Microbiology of Ministry of Education, Fujian Normal University, Fuzhou, ChinaProvincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, ChinaProvincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, ChinaProvincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, ChinaProvincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, ChinaProvincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, ChinaEngineering Research Center of Industrial Microbiology of Ministry of Education, Fujian Normal University, Fuzhou, ChinaBacterial persister cells are phenotypic variants that exhibit transient antibiotic tolerance and play a leading role in chronic infections and the development of antibiotic resistance. Determining the mechanism that underlies persister formation and developing anti-persister strategies, therefore, are clinically important goals. Here, we report that many gram-negative and gram-positive bacteria become highly tolerant to typical bactericidal antibiotics when the carbon source for their antibiotic-sensitive exponential growth phase is shifted to fumarate, suggesting a role for fumarate in persister induction. Nutrient shift-induced Escherichia coli but not Staphylococcus aureus persister cells can be killed by aminoglycosides upon hypoionic shock (i.e., the absence of ions), which is achieved by suspending the persisters in aminoglycoside-containing pure water for only 1 or 2 min. Such potentiation can be abolished by inhibitors of the electron transport chain (e.g., NaN3) or proton motive force (e.g., CCCP). Additionally, we show that hypoionic shock facilitates the eradication of starvation-induced E. coli but not S. aureus persisters by aminoglycosides, and that such potentiation can be significantly suppressed by NaN3 or CCCP. Mechanistically, hypoionic shock dramatically enhances aminoglycoside uptake by both nutrient shift- and starvation-induced E. coli persisters, whereas CCCP can diminish this uptake. Results of our study illustrate the general role of fumarate in bacterial persistence and may open new avenues for persister eradication and aminoglycoside use.https://www.frontiersin.org/article/10.3389/fmicb.2019.02028/fullpersisterantibiotic toleranceaminoglycosideantibiotic uptakefumaratehypoionic shock |
| spellingShingle | Zhongyu Chen Yuanyuan Gao Yuanyuan Gao Boyan Lv Fengqi Sun Wei Yao Yan Wang Xinmiao Fu Xinmiao Fu Hypoionic Shock Facilitates Aminoglycoside Killing of Both Nutrient Shift- and Starvation-Induced Bacterial Persister Cells by Rapidly Enhancing Aminoglycoside Uptake Frontiers in Microbiology persister antibiotic tolerance aminoglycoside antibiotic uptake fumarate hypoionic shock |
| title | Hypoionic Shock Facilitates Aminoglycoside Killing of Both Nutrient Shift- and Starvation-Induced Bacterial Persister Cells by Rapidly Enhancing Aminoglycoside Uptake |
| title_full | Hypoionic Shock Facilitates Aminoglycoside Killing of Both Nutrient Shift- and Starvation-Induced Bacterial Persister Cells by Rapidly Enhancing Aminoglycoside Uptake |
| title_fullStr | Hypoionic Shock Facilitates Aminoglycoside Killing of Both Nutrient Shift- and Starvation-Induced Bacterial Persister Cells by Rapidly Enhancing Aminoglycoside Uptake |
| title_full_unstemmed | Hypoionic Shock Facilitates Aminoglycoside Killing of Both Nutrient Shift- and Starvation-Induced Bacterial Persister Cells by Rapidly Enhancing Aminoglycoside Uptake |
| title_short | Hypoionic Shock Facilitates Aminoglycoside Killing of Both Nutrient Shift- and Starvation-Induced Bacterial Persister Cells by Rapidly Enhancing Aminoglycoside Uptake |
| title_sort | hypoionic shock facilitates aminoglycoside killing of both nutrient shift and starvation induced bacterial persister cells by rapidly enhancing aminoglycoside uptake |
| topic | persister antibiotic tolerance aminoglycoside antibiotic uptake fumarate hypoionic shock |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.02028/full |
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