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. aer...

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Main Authors:	Bomberger, Jennifer M., Ye, Siying, MacEachran, Daniel P., Koeppen, Katja, Barnaby, Roxanna L., O'Toole, George A., Stanton, Bruce A.
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063759/

id	pubmed-3063759
recordtype	oai_dc
spelling	pubmed-30637592011-03-31 A Pseudomonas aeruginosa Toxin that Hijacks the Host Ubiquitin Proteolytic System Bomberger, Jennifer M. Ye, Siying MacEachran, Daniel P. Koeppen, Katja Barnaby, Roxanna L. O'Toole, George A. Stanton, Bruce A. Research Article 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. Public Library of Science 2011-03-24 /pmc/articles/PMC3063759/ /pubmed/21455491 http://dx.doi.org/10.1371/journal.ppat.1001325 Text en Bomberger et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Bomberger, Jennifer M. Ye, Siying MacEachran, Daniel P. Koeppen, Katja Barnaby, Roxanna L. O'Toole, George A. Stanton, Bruce A.
spellingShingle	Bomberger, Jennifer M. Ye, Siying MacEachran, Daniel P. Koeppen, Katja Barnaby, Roxanna L. O'Toole, George A. Stanton, Bruce A. A Pseudomonas aeruginosa Toxin that Hijacks the Host Ubiquitin Proteolytic System
author_facet	Bomberger, Jennifer M. Ye, Siying MacEachran, Daniel P. Koeppen, Katja Barnaby, Roxanna L. O'Toole, George A. Stanton, Bruce A.
author_sort	Bomberger, Jennifer M.
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
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.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063759/
_version_	1611446860043517952

A Pseudomonas aeruginosa Toxin that Hijacks the Host Ubiquitin Proteolytic System

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