Giacomucci, Sean, Alvarez, Laura, Rodrigues, Christopher D. A., Cava, Felipe and Paradis-Bleau, Catherine (2022) Hydroxyl radical overproduction in the envelope : an achilles' heel in peptidoglycan synthesis. Microbiology Spectrum, 10 (1). e0120321. doi:10.1128/spectrum.01203-21 ISSN 2165-0497.

Preview

PDF WRAP-Hydroxyl-radical-overproduction-envelope-Rodrigues-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (5Mb) | Preview

Request Changes to record.

Abstract

While many mechanisms governing bacterial envelope homeostasis have been identified, others remain poorly understood. To decipher these processes, we previously developed an assay in the Gram-negative model Escherichia coli to identify genes involved in maintenance of envelope integrity. One such gene was ElyC, which was shown to be required for envelope integrity and peptidoglycan synthesis at room temperature. ElyC is predicted to be an integral inner membrane protein with a highly conserved domain of unknown function (DUF218). In this study, and stemming from a further characterization of the role of ElyC in maintaining cell envelope integrity, we serendipitously discovered an unappreciated form of oxidative stress in the bacterial envelope. We found that cells lacking ElyC overproduce hydroxyl radicals (HO ) in their envelope compartment and that HO overproduction is directly or indirectly responsible for the peptidoglycan synthesis arrest, cell envelope integrity defects, and cell lysis of the Δ mutant. Consistent with these observations, we show that the Δ mutant defect is suppressed during anaerobiosis. HO is known to cause DNA damage but to our knowledge has not been shown to interfere with peptidoglycan synthesis. Thus, our work implicates oxidative stress as an important stressor in the bacterial cell envelope and opens the door to future studies deciphering the mechanisms that render peptidoglycan synthesis sensitive to oxidative stress. Oxidative stress is caused by the production and excessive accumulation of oxygen reactive species. In bacterial cells, oxidative stress mediated by hydroxyl radicals is typically associated with DNA damage in the cytoplasm. Here, we reveal the existence of a pathway for oxidative stress in the envelope of Gram-negative bacteria. Stemming from the characterization of a poorly characterized gene, we found that HO overproduction specifically in the envelope compartment causes inhibition of peptidoglycan synthesis and eventually bacterial cell lysis.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QP Physiology Q Science > QR Microbiology R Medicine > RB Pathology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
SWORD Depositor:	Library Publications Router
Library of Congress Subject Headings (LCSH):	Oxidative stress , Peptidoglycans -- Synthesis, Microbial metabolism , Active oxygen -- Physiological effect , Hydroxyl group , Homeostasis, Gram-negative bacteria
Journal or Publication Title:	Microbiology Spectrum
Publisher:	American Society for Microbiology
ISSN:	2165-0497
Official Date:	16 February 2022
Dates:	Date Event 16 February 2022 Published 19 January 2022 Accepted
Volume:	10
Number:	1
Article Number:	e0120321
DOI:	10.1128/spectrum.01203-21
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	16 March 2022
Date of first compliant Open Access:	18 March 2022
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID UNSPECIFIED Molecular Infection Medicine Sweden https://www.mims.umu.se/ UNSPECIFIED Vetenskapsrådet http://dx.doi.org/10.13039/501100004359 UNSPECIFIED Kempestiftelserna http://dx.doi.org/10.13039/501100007067 UNSPECIFIED Knut och Alice Wallenbergs Stiftelse http://dx.doi.org/10.13039/501100004063

Request changes or add full text files to a record

Repository staff actions (login required)

View Item

Downloads