Salmonella enteric is a facultative intracellular pathogen that causes a number of diseases including gastroenteritis and typhoid fever. The pathogenesis of Salmonella enteric requires two type III secretion systems (TTSS), specialized organelles that mediate delivery of bacterial virulence effectors proteins from the bacteria to the host cell. Effectors function to promote bacterial survival and colonization. Salmonella typhimurium (S. typhimurium) encodes a family of three leucine-rich repeats (LRR)-containing effectors: SspH1, SspH2, and Slrp. S. typhimurium strains carrying deletion mutations in slrp or in both sspH1 and sspH2 were reduced in virulence in animal models of infection, indicating that these effectors are required for normal pathogenesis. Determining the function of these LRR effectors proteins will provide insights into Salmonella virulence and may lead to the development of novel treatments for Salmonella pathogenesis.
The specific aims are: 1) to determine the spatial and temporal organization of LRR effectors during S. typhimurium infection. 2) To isolate and identify host cell proteins that interacts with S. typhimurium LRR effectors. 3) To elucidate the contribution of LRR effectors in the pathogenesis of S. typhimurium.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI069704-03
Application #
7628536
Study Section
Special Emphasis Panel (ZRG1-F13-P (20))
Program Officer
Alexander, William A
Project Start
2007-06-01
Project End
2010-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
3
Fiscal Year
2009
Total Cost
$53,354
Indirect Cost
Name
Yale University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Zuckerman, David M; Hicks, Stuart W; Charron, Guillaume et al. (2011) Differential regulation of two palmitoylation sites in the cytoplasmic tail of the beta1-adrenergic receptor. J Biol Chem 286:19014-23
Hicks, Stuart W; Charron, Guillaume; Hang, Howard C et al. (2011) Subcellular targeting of Salmonella virulence proteins by host-mediated S-palmitoylation. Cell Host Microbe 10:9-20
Hicks, Stuart W; Galán, Jorge E (2010) Hijacking the host ubiquitin pathway: structural strategies of bacterial E3 ubiquitin ligases. Curr Opin Microbiol 13:41-6
Quezada, Cindy M; Hicks, Stuart W; Galán, Jorge E et al. (2009) A family of Salmonella virulence factors functions as a distinct class of autoregulated E3 ubiquitin ligases. Proc Natl Acad Sci U S A 106:4864-9