Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae

Tools
- Tools
+ Tools

Aggarwal, Surya D. , Lloyd, Adrian J., Yerneni, Saigopalakrishna S., Narciso, Ana Rita, Shepherd, Jennifer, Roper, David I., Dowson, Christopher G., Filipe, Sergio R and Hiller, N Luisa (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). e2018089118. doi:10.1073/pnas.2018089118

[img]
Preview
PDF
WRAP-molecular-link-between-cell-wall-biosynthesis-translation-fidelity-stringent-response-Streptococcus-pneumoniae-Lloyd-2021.pdf - Published Version - Requires a PDF viewer.
Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0.

Download (1505Kb) | Preview
Official URL: https://doi.org/10.1073/pnas.2018089118

Request Changes to record.

Abstract

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-tRNAAlaUGC 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

Item Type: Journal Article
Subjects: Q Science > QR Microbiology
Divisions: Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Streptococcus pneumoniae , Streptococcus pneumoniae -- Effect of drugs on , Bacterial cell walls, Bacterial cell walls -- Synthesis
Journal or Publication Title: Proceedings of the National Academy of Sciences of the United States of America
Publisher: National Academy of Sciences
ISSN: 0027-8424
Official Date: 6 April 2021
Dates:
DateEvent
6 April 2021Published
30 March 2021Available
15 February 2021Accepted
Volume: 118
Number: 14
Article Number: e2018089118
DOI: 10.1073/pnas.2018089118
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Copyright Holders: National Academy of Sciences (USA)
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
R00-DC-011322 National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
Stupakoff Scientific Achievement AwardCarnegie Mellon Universityhttp://dx.doi.org/10.13039/100008047
Glen de Vries Presidential FellowshipMellon College of Science, Carnegie Mellon Universityhttp://dx.doi.org/10.13039/100007063
UNSPECIFIEDEberly Foundationhttp://www.eberlyfoundation.org/
UNSPECIFIEDCarnegie Mellon Universityhttp://dx.doi.org/10.13039/100008047
PTDC/BIA-MIC/30746/2017Fundação para a Ciência e a Tecnologiahttp://dx.doi.org/10.13039/501100001871
UID/Multi/04378/2019Applied Molecular Biosciences UnitUNSPECIFIED
LISBOA-01-0145-FEDER-016417Oneida Nation Foundationhttp://dx.doi.org/10.13039/100003221
G0400848Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G1100127Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/N002679/1 Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
Open Access Version:
  • Publisher

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us