Document Detail


Pseudolipasin A is a specific inhibitor for phospholipase A2 activity of Pseudomonas aeruginosa cytotoxin ExoU.
MedLine Citation:
PMID:  17178785     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A number of bacterial pathogens utilize the type III secretion pathway to deliver effector proteins directly into the host cell cytoplasm. Certain strains of Pseudomonas aeruginosa associated with acute infections express a potent cytotoxin, exoenzyme U (ExoU), that is delivered via the type III secretion pathway directly into contacting host cells. Once inside the mammalian cell, ExoU rapidly lyses the intoxicated cells via its phospholipase A(2) (PLA(2)) activity. A high-throughput cell-based assay was developed to screen libraries of compounds for those capable of protecting cells against the cytotoxic effects of ExoU. A number of compounds were identified in this screen, including one group that blocks the intracellular activity of ExoU. In addition, these compounds specifically inhibited the PLA(2) activity of ExoU in vitro, whereas eukaryotic secreted PLA(2) and cytosolic PLA(2) were not inhibited. This novel inhibitor of ExoU-specific PLA(2) activity, named pseudolipasin A, may provide a new lead for virulence factor-based therapeutic design.
Authors:
Vincent T Lee; Stefan Pukatzki; Hiromi Sato; Eriya Kikawada; Anastasia A Kazimirova; Jin Huang; Xiaohua Li; Jonathan P Arm; Dara W Frank; Stephen Lory
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-12-18
Journal Detail:
Title:  Infection and immunity     Volume:  75     ISSN:  0019-9567     ISO Abbreviation:  Infect. Immun.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-22     Completed Date:  2007-04-10     Revised Date:  2013-11-07    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1089-98     Citation Subset:  IM    
Affiliation:
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. vtlee@umd.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Bacterial Proteins / antagonists & inhibitors*,  biosynthesis,  genetics,  physiology
CHO Cells
Cricetinae
Cricetulus
Cytotoxins / antagonists & inhibitors*,  biosynthesis,  genetics,  physiology
Enzyme Inhibitors / pharmacology*
Fluorenes / chemistry,  pharmacology*
Phospholipases A / antagonists & inhibitors*
Phospholipases A2
Pseudomonas aeruginosa / enzymology*,  genetics,  physiology
Virulence Factors / antagonists & inhibitors,  biosynthesis,  genetics,  physiology
Grant Support
ID/Acronym/Agency:
K22 AI065828/AI/NIAID NIH HHS; R01-AI49577/AI/NIAID NIH HHS; R01-HL070946/HL/NHLBI NIH HHS; R21-HL079393/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Cytotoxins; 0/Enzyme Inhibitors; 0/Fluorenes; 0/Virulence Factors; 0/pseudolipasin A; 0/pseudomonas exoprotein A protein, Pseudomonas aeruginosa; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Phospholipases A2
Comments/Corrections

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