The mechanism of action of the XXXX -encoded type III cytotoxin, ExoU.

@entity1 @entity137 @entity796 @entity13312 @entity30076 @entity2348 @entity651 @entity281 @entity460 @entity375 @entity7609
@entity796 delivers the toxin ExoU to eukaryotic cells via a type III secretion system. Intoxication with ExoU is associated with @entity651 , @entity2348 in animal model and @entity1 @entity281 . To search for ExoU targets in a genetically tractable system, we used controlled expression of the toxin in @entity375 . ExoU was cytotoxic for @entity375 and caused a @entity13312 phenotype. Inhibitors of @entity1 @entity460 -independent ( @entity30076 ) and cytosolic phospholipase A(2) (cPLA(2)) lipase activity reduce the @entity137 of ExoU. The catalytic domains of patatin, @entity30076 and cPLA(2) align or are similar to ExoU sequences. Site-specific mutagenesis of predicted catalytic residues (ExoUS142A or ExoUD344A) eliminated @entity137 . ExoU expression in @entity375 resulted in an accumulation of free @entity7609 , changes in the phospholipid profiles and reduction of radiolabeled neutral lipids. ExoUS142A and ExoUD344A expressed in @entity375 failed to release @entity7609 . Recombinant ExoU demonstrated lipase activity in vitro, but only in the presence of a @entity375 extract. From these data we conclude that ExoU is a lipase that requires activation or modification by eukaryotic factors.
