Document Detail


The Pseudomonas aeruginosa PhoP-PhoQ two-component regulatory system is induced upon interaction with epithelial cells and controls cytotoxicity and inflammation.
MedLine Citation:
PMID:  22710876     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The adaptation of Pseudomonas aeruginosa to its environment, including the host, is tightly controlled by its network of regulatory systems. The two-component regulatory system PhoPQ has been shown to play a role in the virulence and polymyxin resistance of P. aeruginosa as well as several other Gram-negative species. Dysregulation of this system has been demonstrated in clinical isolates, yet how it affects virulence of P. aeruginosa is unknown. To investigate this, an assay was used whereby bacteria were cocultured with human bronchial epithelial cells. The interaction of wild-type (WT) bacteria that had adhered to epithelial cells led to a large upregulation of the expression of the oprH-phoP-phoQ operon and its target, the arn lipopolysaccharide (LPS) modification operon, in a PhoQ-dependent manner, compared to cells in the supernatant that had failed to adhere. Relative to the wild type, a phoQ mutant cocultured on epithelial cells produced less secreted protease and lipase and, like the phoQ mutant, piv, lipH, and lasB mutants demonstrated reduced cytotoxicity toward epithelial cells. Mutation in phoQ also resulted in alterations to lipid A and to increased inflammatory LPS. These data indicate that mutation of phoQ results in a phenotype that is similar to the less virulent but more inflammatory phenotype of clinical strains isolated from chronic-stage cystic fibrosis lung infections.
Authors:
Shaan L Gellatly; Brittany Needham; Laurence Madera; M Stephen Trent; Robert E W Hancock
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-18
Journal Detail:
Title:  Infection and immunity     Volume:  80     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-15     Completed Date:  2012-10-24     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3122-31     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology and Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, British Columbia, Canada.
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MeSH Terms
Descriptor/Qualifier:
Bacterial Adhesion
Bacterial Proteins / genetics,  metabolism*
Cell Line
Epithelial Cells / microbiology*
Gene Expression Regulation, Bacterial*
Host-Pathogen Interactions*
Humans
Inflammation
Mutation
Pseudomonas aeruginosa / genetics*,  pathogenicity*
Grant Support
ID/Acronym/Agency:
AI064184/AI/NIAID NIH HHS; AI76322/AI/NIAID NIH HHS; R01 AI064184/AI/NIAID NIH HHS; //Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/PhoQ protein, Bacteria; 125360-99-8/PhoP protein, Bacteria
Comments/Corrections

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