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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Autores principales:	Tao Xu, Xuyang Wang, Lu Meng, Mengqi Zhu, Jing Wu, Yuanyuan Xu, Ying Zhang, Wenhong Zhang
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	ATP Staphylococcus aureus antibiotic persistence magnesium Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/410a3043acde49a09d4e30d0eef192f8
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spelling	oai:doaj.org-article:410a3043acde49a09d4e30d0eef192f82021-11-15T15:27:54ZMagnesium Links Starvation-Mediated Antibiotic Persistence to ATP10.1128/mSphere.00862-192379-5042https://doaj.org/article/410a3043acde49a09d4e30d0eef192f82020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00862-19https://doaj.org/toc/2379-5042ABSTRACT 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.Tao XuXuyang WangLu MengMengqi ZhuJing WuYuanyuan XuYing ZhangWenhong ZhangAmerican Society for MicrobiologyarticleATPStaphylococcus aureusantibiotic persistencemagnesiumMicrobiologyQR1-502ENmSphere, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	ATP Staphylococcus aureus antibiotic persistence magnesium Microbiology QR1-502
spellingShingle	ATP Staphylococcus aureus antibiotic persistence magnesium Microbiology QR1-502 Tao Xu Xuyang Wang Lu Meng Mengqi Zhu Jing Wu Yuanyuan Xu Ying Zhang Wenhong Zhang Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP
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.
format	article
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
title	Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP
title_short	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_sort	magnesium links starvation-mediated antibiotic persistence to atp
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/410a3043acde49a09d4e30d0eef192f8
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Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP

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