A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen chronically infecting the lungs of patients with chronic obstructive pulmonary disease (COPD), pneumonia, cystic fibrosis (CF), and bronchiectasis. Cif (PA2934), a bacterial toxin secreted in outer membrane vesicles (OMV) by P. aeru...

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Auteurs principaux: Jennifer M Bomberger, Siying Ye, Daniel P Maceachran, Katja Koeppen, Roxanna L Barnaby, George A O'Toole, Bruce A Stanton
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Langue:EN
Publié: Public Library of Science (PLoS) 2011
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Accès en ligne:https://doaj.org/article/056d8f81590b4b6a92ec79bf107cbb57
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spelling oai:doaj.org-article:056d8f81590b4b6a92ec79bf107cbb572021-11-18T06:03:30ZA Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.1553-73661553-737410.1371/journal.ppat.1001325https://doaj.org/article/056d8f81590b4b6a92ec79bf107cbb572011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21455491/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen chronically infecting the lungs of patients with chronic obstructive pulmonary disease (COPD), pneumonia, cystic fibrosis (CF), and bronchiectasis. Cif (PA2934), a bacterial toxin secreted in outer membrane vesicles (OMV) by P. aeruginosa, reduces CFTR-mediated chloride secretion by human airway epithelial cells, a key driving force for mucociliary clearance. The aim of this study was to investigate the mechanism whereby Cif reduces CFTR-mediated chloride secretion. Cif redirected endocytosed CFTR from recycling endosomes to lysosomes by stabilizing an inhibitory effect of G3BP1 on the deubiquitinating enzyme (DUB), USP10, thereby reducing USP10-mediated deubiquitination of CFTR and increasing the degradation of CFTR in lysosomes. This is the first example of a bacterial toxin that regulates the activity of a host DUB. These data suggest that the ability of P. aeruginosa to chronically infect the lungs of patients with COPD, pneumonia, CF, and bronchiectasis is due in part to the secretion of OMV containing Cif, which inhibits CFTR-mediated chloride secretion and thereby reduces the mucociliary clearance of pathogens.Jennifer M BombergerSiying YeDaniel P MaceachranKatja KoeppenRoxanna L BarnabyGeorge A O'TooleBruce A StantonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 3, p e1001325 (2011)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Jennifer M Bomberger
Siying Ye
Daniel P Maceachran
Katja Koeppen
Roxanna L Barnaby
George A O'Toole
Bruce A Stanton
A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.
description Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen chronically infecting the lungs of patients with chronic obstructive pulmonary disease (COPD), pneumonia, cystic fibrosis (CF), and bronchiectasis. Cif (PA2934), a bacterial toxin secreted in outer membrane vesicles (OMV) by P. aeruginosa, reduces CFTR-mediated chloride secretion by human airway epithelial cells, a key driving force for mucociliary clearance. The aim of this study was to investigate the mechanism whereby Cif reduces CFTR-mediated chloride secretion. Cif redirected endocytosed CFTR from recycling endosomes to lysosomes by stabilizing an inhibitory effect of G3BP1 on the deubiquitinating enzyme (DUB), USP10, thereby reducing USP10-mediated deubiquitination of CFTR and increasing the degradation of CFTR in lysosomes. This is the first example of a bacterial toxin that regulates the activity of a host DUB. These data suggest that the ability of P. aeruginosa to chronically infect the lungs of patients with COPD, pneumonia, CF, and bronchiectasis is due in part to the secretion of OMV containing Cif, which inhibits CFTR-mediated chloride secretion and thereby reduces the mucociliary clearance of pathogens.
format article
author Jennifer M Bomberger
Siying Ye
Daniel P Maceachran
Katja Koeppen
Roxanna L Barnaby
George A O'Toole
Bruce A Stanton
author_facet Jennifer M Bomberger
Siying Ye
Daniel P Maceachran
Katja Koeppen
Roxanna L Barnaby
George A O'Toole
Bruce A Stanton
author_sort Jennifer M Bomberger
title A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.
title_short A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.
title_full A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.
title_fullStr A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.
title_full_unstemmed A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.
title_sort pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/056d8f81590b4b6a92ec79bf107cbb57
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