气候变化领域集成服务门户(CCPortal): Staphylococcal ClpXP protease targets the cellular antioxidant system to eliminate fitness-compromised cells in stationary phase

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DOI	10.1073/pnas.2109671118
	Staphylococcal ClpXP protease targets the cellular antioxidant system to eliminate fitness-compromised cells in stationary phase
	Alqarzaee A.A.; Chaudhari S.S.; Islam M.M.; Kumar V.; Zimmerman M.C.; Saha R.; Bayles K.W.; Frees D.; Thomas V.C.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:47
英文摘要	The transition from growth to stationary phase is a natural response of bacteria to starvation and stress. When stress is alleviated and more favorable growth conditions return, bacteria resume proliferation without a significant loss in fitness. Although specific adaptations that enhance the persistence and survival of bacteria in stationary phase have been identified, mechanisms that help maintain the competitive fitness potential of nondividing bacterial populations have remained obscure. Here, we demonstrate that staphylococci that enter stationary phase following growth in media supplemented with excess glucose, undergo regulated cell death to maintain the competitive fitness potential of the population. Upon a decrease in extracellular pH, the acetate generated as a byproduct of glucose metabolism induces cytoplasmic acidification and extensive protein damage in nondividing cells. Although cell death ensues, it does not occur as a passive consequence of protein damage. Instead, we demonstrate that the expression and activity of the ClpXP protease is induced, resulting in the degeneration of cellular antioxidant capacity and, ultimately, cell death. Under these conditions, inactivation of either clpX or clpP resulted in the extended survival of unfit cells in stationary phase, but at the cost of maintaining population fitness. Finally, we show that cell death from antibiotics that interfere with bacterial protein synthesis can also be partly ascribed to the corresponding increase in clpP expression and activity. The functional conservation of ClpP in eukaryotes and bacteria suggests that ClpP-dependent cell death and fitness maintenance may be a widespread phenomenon in these domains of life. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	ClpP; ClpX; SodA; Staphylococcus aureus; Stationary phase fitness
语种	英语
scopus关键词	acetic acid; antibiotic agent; bacterial enzyme; ClpXP protein; endopeptidase Clp; endopeptidase ClpX; glucose; proteinase; unclassified drug; antioxidant; bacterial protein; endopeptidase Clp; acidification; Article; bacterial cell; bacterial growth; bacterial viability; cellular antioxidant system; cellular parameters; cytoplasm; enzyme activity; enzyme inactivation; glucose metabolism; immobilized cell; microbial competition; nonhuman; pH; protein expression; protein synthesis; regulated cell death; Staphylococcus; bacterium; cell death; enzymology; gene expression regulation; genetics; metabolism; Staphylococcus aureus; Acetic Acid; Antioxidants; Bacteria; Bacterial Proteins; Cell Death; Endopeptidase Clp; Gene Expression Regulation, Bacterial; Glucose; Staphylococcus aureus
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/250980
作者单位	Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, United States; Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, NE 68588, United States; Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, United States; Mass Spectrometry and Proteomics Core Facility, University of Nebraska Medical Center, Omaha, NE 68198, United States; Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, United States; Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, 1870, Denmark
推荐引用方式 GB/T 7714	Alqarzaee A.A.,Chaudhari S.S.,Islam M.M.,et al. Staphylococcal ClpXP protease targets the cellular antioxidant system to eliminate fitness-compromised cells in stationary phase[J],2021,118(47).
APA	Alqarzaee A.A..,Chaudhari S.S..,Islam M.M..,Kumar V..,Zimmerman M.C..,...&Thomas V.C..(2021).Staphylococcal ClpXP protease targets the cellular antioxidant system to eliminate fitness-compromised cells in stationary phase.Proceedings of the National Academy of Sciences of the United States of America,118(47).
MLA	Alqarzaee A.A.,et al."Staphylococcal ClpXP protease targets the cellular antioxidant system to eliminate fitness-compromised cells in stationary phase".Proceedings of the National Academy of Sciences of the United States of America 118.47(2021).