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DOI	10.1073/pnas.2106022118
	Demonstration of the role of cell wall homeostasis in Staphylococcus aureus growth and the action of bactericidal antibiotics
	Salamaga B.; Kong L.; Pasquina-Lemonche L.; Lafage L.; Von Und Zur Muhlen M.; Gibson J.F.; Grybchuk D.; Tooke A.K.; Panchal V.; Culp E.J.; Tatham E.; O'Kane M.E.; Catley T.E.; Renshaw S.A.; Wright G.D.; Plevka P.; Bullough P.A.; Han A.; Hobbs J.K.; Foster S.J.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:44
英文摘要	Bacterial cell wall peptidoglycan is essential, maintaining both cellular integrity and morphology, in the face of internal turgor pressure. Peptidoglycan synthesis is important, as it is targeted by cell wall antibiotics, including methicillin and vancomycin. Here, we have used the major human pathogen Staphylococcus aureus to elucidate both the cell wall dynamic processes essential for growth (life) and the bactericidal effects of cell wall antibiotics (death) based on the principle of coordinated peptidoglycan synthesis and hydrolysis. The death of S. aureus due to depletion of the essential, two-component and positive regulatory system for peptidoglycan hydrolase activity (WalKR) is prevented by addition of otherwise bactericidal cell wall antibiotics, resulting in stasis. In contrast, cell wall antibiotics kill via the activity of peptidoglycan hydrolases in the absence of concomitant synthesis. Both methicillin and vancomycin treatment lead to the appearance of perforating holes throughout the cell wall due to peptidoglycan hydrolases. Methicillin alone also results in plasmolysis and misshapen septa with the involvement of the major peptidoglycan hydrolase Atl, a process that is inhibited by vancomycin. The bactericidal effect of vancomycin involves the peptidoglycan hydrolase SagB. In the presence of cell wall antibiotics, the inhibition of peptidoglycan hydrolase activity using the inhibitor complestatin results in reduced killing, while, conversely, the deregulation of hydrolase activity via loss of wall teichoic acids increases the death rate. For S. aureus, the independent regulation of cell wall synthesis and hydrolysis can lead to cell growth, death, or stasis, with implications for the development of new control regimes for this important pathogen. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antibiotics; Cell wall; Methicillin; Peptidoglycan; Vancomycin
语种	英语
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/238319
作者单位	School of Biosciences, University of Sheffield, Sheffield, S102TN, United Kingdom; The Florey Institute for Host-Pathogen Interactions, University of Sheffield, Sheffield, S102TN, United Kingdom; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China; Department of Physics and Astronomy, University of Sheffield, Sheffield, S37RH, United Kingdom; The Bateson Centre, University of Sheffield, Sheffield, S102TN, United Kingdom; Central European Institute of Technology, Masaryk University, Brno, 60177, Czech Republic; M. G. DeGroote Institute for Infectious Disease Research, David Braley Centre for Antibiotic Discovery, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S4L8, Canada; Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield, Sheffield, S102RX, United Kingdom
推荐引用方式 GB/T 7714	Salamaga B.,Kong L.,Pasquina-Lemonche L.,et al. Demonstration of the role of cell wall homeostasis in Staphylococcus aureus growth and the action of bactericidal antibiotics[J],2021,118(44).
APA	Salamaga B..,Kong L..,Pasquina-Lemonche L..,Lafage L..,Von Und Zur Muhlen M..,...&Foster S.J..(2021).Demonstration of the role of cell wall homeostasis in Staphylococcus aureus growth and the action of bactericidal antibiotics.Proceedings of the National Academy of Sciences of the United States of America,118(44).
MLA	Salamaga B.,et al."Demonstration of the role of cell wall homeostasis in Staphylococcus aureus growth and the action of bactericidal antibiotics".Proceedings of the National Academy of Sciences of the United States of America 118.44(2021).