文章基本信息

标题：A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae
本地全文：下载
作者：Surya D. Aggarwal ; Adrian J. Lloyd ; Saigopalakrishna S. Yerneni 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：14
页码：1
DOI：10.1073/pnas.2018089118
出版社：The National Academy of Sciences of the United States of America
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 Δ murMN strain displays growth arrest and extensive lysis. Furthermore, these stress conditions compromise the efficiency with which alanyl-tRNA Ala synthetase can avoid noncognate mischarging of tRNA Ala 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-tRNA Ala synthetase that enables detoxification of tRNA misacylation. Furthermore, MurM can incorporate seryl groups from mischarged Seryl-tRNA Ala 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 Δ murMN 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-tRNA Ala by MurM may represent a first line of defense. When this mechanism is overwhelmed or absent (Δ murMN ), the stringent response shuts down translation to avoid toxic generation of mistranslated/misfolded proteins.
关键词：Streptococcus pneumoniae ; cell wall ; translation quality control ; stringent response ; autolysis