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Hydroxyl Radical Overproduction in the Envelope: An Achilles' Heel in Peptidoglycan Synthesis
Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, QC, Montréal, Canada.
Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).ORCID-id: 0000-0003-2429-7542
iThree Institute, University of Technology Sydney, NSW, Ultimo, Australia; School of Life Sciences, University of Warwick, Coventry, United Kingdom.
Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).ORCID-id: 0000-0001-5995-718x
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2022 (Engelska)Ingår i: Microbiology Spectrum, E-ISSN 2165-0497, Vol. 10, nr 1, artikel-id e01203-21Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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 DelyC mutant. Consistent with these observations, we show that the DelyC mutant defect is suppressed during anaerobiosis. HOis 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.

Ort, förlag, år, upplaga, sidor
American Society for Microbiology , 2022. Vol. 10, nr 1, artikel-id e01203-21
Nyckelord [en]
Bacterial envelope biology, Fenton reaction, Hydroxyl radical, Iron homeostasis, Oxidative stress, Peptidoglycan, Peptidoglycan synthesis, Reactive oxygen species
Nationell ämneskategori
Mikrobiologi Mikrobiologi inom det medicinska området
Identifikatorer
URN: urn:nbn:se:umu:diva-192948DOI: 10.1128/spectrum.01203-21ISI: 000766015800047PubMedID: 35170991Scopus ID: 2-s2.0-85125212717OAI: oai:DiVA.org:umu-192948DiVA, id: diva2:1643032
Forskningsfinansiär
Knut och Alice Wallenbergs StiftelseVetenskapsrådetKempestiftelsernaTillgänglig från: 2022-03-08 Skapad: 2022-03-08 Senast uppdaterad: 2023-10-06Bibliografiskt granskad

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Alvarez, LauraCava, Felipe

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Molekylär Infektionsmedicin, Sverige (MIMS)Umeå Centre for Microbial Research (UCMR)
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