Toxin production is essential for the virulence of Vibrio cholerae and the pathogenesis of cholera disease. Epidemiological data indicate an increased prevalence of pathogenic strains defective in the production of cholera toxin. Reactogenic symptoms are attributed to a number of accessory toxins, including the V. cholerae RTX toxin. However, unlike the other members of the RTX family, RtxA is not a pore-forming toxin. RtxA activity promotes host cell rounding, and actin monomers are covalently cross-linked through a completely novel mechanism. Understanding the individual components of the cross-linking reaction is the focus of this proposal. Cytoskeletal inhibition will define the actin substrate, the characterization of a putative enzymatic domain may identify a catalytic function of RtxA, and a combined biochemical and genetic approach will reveal the chemical properties of the linkage between actin monomers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31AI052490-01
Application #
6546205
Study Section
Special Emphasis Panel (ZRG1-F05 (29))
Program Officer
Hernandez, Milton J
Project Start
2002-07-01
Project End
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
1
Fiscal Year
2002
Total Cost
$24,986
Indirect Cost
Name
Northwestern University at Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Kudryashov, Dmitri S; Cordero, Christina L; Reisler, Emil et al. (2008) Characterization of the enzymatic activity of the actin cross-linking domain from the Vibrio cholerae MARTX Vc toxin. J Biol Chem 283:445-52
Cordero, Christina L; Sozhamannan, Shanmuga; Satchell, Karla J Fullner (2007) RTX toxin actin cross-linking activity in clinical and environmental isolates of Vibrio cholerae. J Clin Microbiol 45:2289-92
Sheahan, Kerri-Lynn; Cordero, Christina L; Satchell, Karla J Fullner (2004) Identification of a domain within the multifunctional Vibrio cholerae RTX toxin that covalently cross-links actin. Proc Natl Acad Sci U S A 101:9798-803