Pseudomonas Aeruginosa ExoS and ExoT

Rev Physiol Biochem Pharmacol. 2004;152:79-92. doi: 10.1007/s10254-004-0031-7. Epub 2004 Aug 24.

Abstract

ExoS and ExoT are bi-functional type-III cytotoxins of Pseudomonas aeruginosa that share 76% primary amino acid homology and contain N-terminal RhoGAP domains and C-terminal ADP-ribosylation domains. The Rho GAP activities of ExoS and ExoT appear to be biochemically and biologically identical, targeting Rho, Rac, and Cdc42. Expression of the RhoGAP domain in mammalian cells results in the disruption of the actin cytoskeleton and interference of phagocytosis. Expression of the ADP-ribosyltransferase domain of ExoS elicits a cytotoxic phenotype in cultured cells, while expression of ExoT appears to interfere with host cell phagocytic activity. Recent studies showed that ExoS and ExoT ADP-ribosylate different substrates. While ExoS has poly-substrate specificity and can ADP-ribosylate numerous host proteins, ExoT ADP-ribosylates a more restricted subset of host proteins including the Crk proteins. Protein modeling predicts that electrostatic interactions contribute to the substrate specificity of the ADP-ribosyltransferase domains of ExoS and ExoT.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • ADP Ribose Transferases / chemistry
  • ADP Ribose Transferases / metabolism*
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / metabolism*
  • Cell Membrane / enzymology
  • Evolution, Molecular
  • GTPase-Activating Proteins
  • Models, Molecular
  • Phagocytosis
  • Protein Conformation
  • Pseudomonas aeruginosa / metabolism*

Substances

  • Bacterial Toxins
  • ExoT protein, Pseudomonas aeruginosa
  • GTPase-Activating Proteins
  • ADP Ribose Transferases
  • exoenzyme S