The goal of this research is to identify genes and pathways of mammalian host that play a role during Pseudomonas infections. Specifically, the mechanism of action of a class of proteins produced by Pseudomonas aeruginosa, an opportunistic pathogen of immuno- compromised patients, will be studied. These proteins act by distinct intracellular mechanisms in the host cell, but share a common delivery mechanism. Four proteins, exoenzymes S, Y, T and U (ExoS, T, Y and U) are produced by most clinical isolates of P. aeruginosa and are delivered into mammalian cells by a contact-dependent mechanism, called the Type II secretion pathway. Once in the host, these exoenzymes manipulate host signal transduction pathways eventually leading to either host cell cytotoxicity or apoptosis. The host factors that are involved in the delivery and activation of these toxins are not well characterized. This proposal aims to combine the newly developed tools of mammalian somatic cell genetics and the availability of the mammalian genomes to identify host factors that contribute to the function of ExoS, T, Y and U, starting with their export by the bacterial type III secretion machinery to their final site of activity in the mammalian cell cytoplasm.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI052694-03
Application #
6751332
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Taylor, Christopher E,
Project Start
2002-07-01
Project End
2005-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
3
Fiscal Year
2004
Total Cost
$48,928
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115