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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. and Stanton, Bruce A. 2011, A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system, PL o S pathogens, vol. 7, no. 3, pp. 1-13, doi: 10.1371/journal.ppat.1001325.

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Title A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system
Formatted title A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system
Author(s) Bomberger, Jennifer M.
Ye, SiyingORCID iD for Ye, Siying orcid.org/0000-0002-0882-1642
MacEachran, Daniel P.
Koeppen, Katja
Barnaby, Roxanna L.
O'Toole, George A.
Stanton, Bruce A.
Journal name PL o S pathogens
Volume number 7
Issue number 3
Article ID e1001325
Start page 1
End page 13
Total pages 13
Publisher Public Library of Science
Place of publication San Francisco, Calif.
Publication date 2011-03
ISSN 1553-7366
1553-7374
Keyword(s) bacterial toxin
bacterial toxin Cif
binding protein
chloride
enzyme
protein USP10
Ras GAP SH3 domain binding protein 1
small interfering RNA
transmembrane conductance regulator
ubiquitin
unclassified drug
Summary 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.
Language eng
DOI 10.1371/journal.ppat.1001325
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2011, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30040950

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.