A Pseudomonas aeruginosa Toxin that Hijacks the Host Ubiquitin Proteolytic System

• DOI: 10.1371/journal.ppat.1001325
• Publication Date: 2011-03-24T20:55:46Z
• Authors: Jennifer M. Bombe...; Siying Ye; Daniel P. MacEachran; Katja Koeppen; Roxanna L. Barnaby; George A. O'Toole; Bruce A. Stanton
• Keywords: Mucociliary clearance; Deubiquitinating enzyme

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 human airway epithelial cells, key driving force for mucociliary clearance. The aim this study was to investigate mechanism whereby secretion. redirected endocytosed CFTR from recycling endosomes lysosomes stabilizing inhibitory effect G3BP1 on deubiquitinating enzyme (DUB), USP10, thereby reducing USP10-mediated deubiquitination increasing degradation lysosomes. This first example that regulates activity host DUB. These data suggest ability infect COPD, CF, bronchiectasis due part OMV containing Cif, which inhibits clearance pathogens.