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DOI	10.1073/pnas.2018089118
	A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae
	Aggarwal S.D.; Lloyd A.J.; Yerneni S.S.; Narciso A.R.; Shepherd J.; Roper D.I.; Dowson C.G.; Filipe S.R.; Hiller N.L.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	Survival in the human host requires bacteria to respond to unfavorable conditions. In the important Gram-positive pathogen Streptococcus pneumoniae, cell wall biosynthesis proteins MurM and MurN are tRNA-dependent amino acyl transferases which lead to the production of branched muropeptides. We demonstrate that wild-type cells experience optimal growth under mildly acidic stressed conditions, but ΔmurMN strain displays growth arrest and extensive lysis. Furthermore, these stress conditions compromise the efficiency with which alanyl-tRNAAla synthetase can avoid noncognate mischarging of tRNAAla with serine, which is toxic to cells. The observed growth defects are rescued by inhibition of the stringent response pathway or by overexpression of the editing domain of alanyl-tRNAAla synthetase that enables detoxification of tRNA misacylation. Furthermore, MurM can incorporate seryl groups from mischarged Seryl-tRNAAla UGC into cell wall precursors with exquisite specificity. We conclude that MurM contributes to the fidelity of translation control and modulates the stress response by decreasing the pool of mischarged tRNAs. Finally, we show that enhanced lysis of ΔmurMN pneumococci is caused by LytA, and the murMN operon influences macrophage phagocytosis in a LytA-dependent manner. Thus, MurMN attenuates stress responses with consequences for host-pathogen interactions. Our data suggest a causal link between misaminoacylated tRNA accumulation and activation of the stringent response. In order to prevent potential corruption of translation, consumption of seryl-tRNAAla by MurM may represent a first line of defense. When this mechanism is overwhelmed or absent (ΔmurMN), the stringent response shuts down translation to avoid toxic generation of mistranslated/misfolded proteins. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autolysis; Cell wall; Streptococcus pneumoniae; Stringent response; Translation quality control
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/180004
作者单位	Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, United States; School of Life Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, United States; Laboratory of Bacterial Cell Surfaces and Pathogenesis, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, 1099-085, Portugal; Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, 2825-149, Portugal
推荐引用方式 GB/T 7714	Aggarwal S.D.,Lloyd A.J.,Yerneni S.S.,et al. A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae[J],2021,118(14).
APA	Aggarwal S.D..,Lloyd A.J..,Yerneni S.S..,Narciso A.R..,Shepherd J..,...&Hiller N.L..(2021).A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Aggarwal S.D.,et al."A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).