ExoU is an acutely cytotoxic protein that is secreted by Pseudomonas aeruginosa via a type III secretion system directly into mammalian cells. P. aeruginosa is an opportunistic pathogen that infects immunocompromised individuals and patients with cystic fibrosis. In cystic fibrosis patients the expression of ExoU has been correlated with damage to the lungs and ability of the bacteria to disseminate to the blood stream. The mechanism of cytotoxicity of ExoU is unknown. Previous studies have shown that secretion of ExoU requires a specific chaperone, SpcU. Determination of the crystal structure of ExoU, alone and bound to it's chaperone, as described in this proposal, will help to understand the function of ExoU and the important role of chaperones in type III secretion. The structural studies combined with the proposed studies of the enzymatic activity of ExoU will help to determine the mechanism of cytotoxicity of this protein.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI049669-02
Application #
6511379
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Korpela, Jukka K
Project Start
2002-03-01
Project End
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
2
Fiscal Year
2002
Total Cost
$44,212
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Biochemistry
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109