Pseudolipasin A Is a Specific Inhibitor for Phospholipase A 2 Activity of Pseudomonas aeruginosa Cytotoxin ExoU
- 1 March 2007
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 75 (3), 1089-1098
- https://doi.org/10.1128/iai.01184-06
Abstract
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.Keywords
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