In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 9 ( 2021-9-13), p. e1009927-
Abstract:
Regulated cell necrosis supports immune and anti-infectious strategies of the body; however, dysregulation of these processes drives pathological organ damage. Pseudomonas aeruginosa expresses a phospholipase, ExoU that triggers pathological host cell necrosis through a poorly characterized pathway. Here, we investigated the molecular and cellular mechanisms of ExoU-mediated necrosis. We show that cellular peroxidised phospholipids enhance ExoU phospholipase activity, which drives necrosis of immune and non-immune cells. Conversely, both the endogenous lipid peroxidation regulator GPX4 and the pharmacological inhibition of lipid peroxidation delay ExoU-dependent cell necrosis and improve bacterial elimination in vitro and in vivo . Our findings also pertain to the ExoU-related phospholipase from the bacterial pathogen Burkholderia thailandensis , suggesting that exploitation of peroxidised phospholipids might be a conserved virulence mechanism among various microbial phospholipases. Overall, our results identify an original lipid peroxidation-based virulence mechanism as a strong contributor of microbial phospholipase-driven pathology.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009927
DOI:
10.1371/journal.ppat.1009927.g001
DOI:
10.1371/journal.ppat.1009927.g002
DOI:
10.1371/journal.ppat.1009927.g003
DOI:
10.1371/journal.ppat.1009927.g004
DOI:
10.1371/journal.ppat.1009927.t001
DOI:
10.1371/journal.ppat.1009927.s001
DOI:
10.1371/journal.ppat.1009927.s002
DOI:
10.1371/journal.ppat.1009927.s003
DOI:
10.1371/journal.ppat.1009927.s004
DOI:
10.1371/journal.ppat.1009927.s005
DOI:
10.1371/journal.ppat.1009927.s006
DOI:
10.1371/journal.ppat.1009927.s007
DOI:
10.1371/journal.ppat.1009927.s008
DOI:
10.1371/journal.ppat.1009927.s009
DOI:
10.1371/journal.ppat.1009927.s010
DOI:
10.1371/journal.ppat.1009927.s011
DOI:
10.1371/journal.ppat.1009927.s012
DOI:
10.1371/journal.ppat.1009927.s013
DOI:
10.1371/journal.ppat.1009927.s014
DOI:
10.1371/journal.ppat.1009927.s015
DOI:
10.1371/journal.ppat.1009927.s016
DOI:
10.1371/journal.ppat.1009927.s017
DOI:
10.1371/journal.ppat.1009927.s018
DOI:
10.1371/journal.ppat.1009927.s019
DOI:
10.1371/journal.ppat.1009927.s020
DOI:
10.1371/journal.ppat.1009927.s021
DOI:
10.1371/journal.ppat.1009927.r001
DOI:
10.1371/journal.ppat.1009927.r002
DOI:
10.1371/journal.ppat.1009927.r003
DOI:
10.1371/journal.ppat.1009927.r004
DOI:
10.1371/journal.ppat.1009927.r005
DOI:
10.1371/journal.ppat.1009927.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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