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Pseudomonas aeruginosa ExoS and ExoT
1Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plk. Road, Milwaukee, WI 53226, USA. jtb01@mcw.edu
Reviews of Physiology, Biochemistry and Pharmacology
|September 18, 2004
Summary
Pseudomonas aeruginosa cytotoxins ExoS and ExoT disrupt host cells via RhoGAP and ADP-ribosylation. While their RhoGAP functions are identical, their ADP-ribosylation targets differ, impacting host cell activity.
Area of Science:
- Microbiology
- Molecular Biology
- Cell Biology
Background:
- Pseudomonas aeruginosa utilizes type-III secreted toxins, ExoS and ExoT, to manipulate host cells.
- These toxins share structural homology, possessing RhoGAP and ADP-ribosylation domains.
Purpose of the Study:
- To elucidate the distinct roles and substrate specificities of ExoS and ExoT in host cell modulation.
- To investigate the functional differences between the ADP-ribosyltransferase domains of ExoS and ExoT.
Main Methods:
- Expression of ExoS and ExoT domains in mammalian cells.
- Biochemical assays to assess RhoGAP and ADP-ribosylation activities.
- Protein modeling to predict substrate interactions.
Main Results:
- Both ExoS and ExoT RhoGAP domains disrupt the actin cytoskeleton and inhibit phagocytosis.
- ExoS ADP-ribosyltransferase domain is cytotoxic, while ExoT interferes with phagocytosis.
- ExoS targets a broad range of proteins, whereas ExoT specifically targets proteins like Crk.
Conclusions:
- ExoS and ExoT exhibit distinct functions beyond their shared RhoGAP activity.
- Differences in ADP-ribosylation substrate specificity contribute to the varied biological effects of ExoS and ExoT.
- Protein modeling suggests electrostatic interactions govern ADP-ribosyltransferase domain specificity.