A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system
Data(s) |
01/03/2011
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Resumo |
<i>Pseudomonas aeruginosa</i> (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 <i>P. aeruginosa</i> 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. |
Identificador | |
Idioma(s) |
eng |
Publicador |
Public Library of Science |
Relação |
http://dro.deakin.edu.au/eserv/DU:30040950/ye-pseudomonasaeruginosa-2007.pdf http://dx.doi.org/10.1371/journal.ppat.1001325 |
Direitos |
2011, PLoS |
Palavras-Chave | #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 |
Tipo |
Journal Article |