Coxiella burnetii is an intracellular pathogen that causes the human disease Q-fever. Mechanisms by which this bacterial pathogen exploits human cells remain unknown. This project is focused on identifying key virulence determinants in Coxiella and determining how these factors promote infection. The Coxiella Dot/Icm system is a functional protein secretion machine that promotes infection by delivering bacterial effectors into host cells. We have identified Coxiella effector proteins and host proteins important for infection. To understand the interface between these bacterial determinants and host proteins the following specific aims will be completed.
Aim 1) Identify Coxiella effectors and host factors required for infection using genome-wide screening approaches.
Aim 2) Determine the role of the Coxiella Dot/Icm system during infection and identify bacterial determinants required for intracellular replication.
Aim 3) Elucidate the function of Coxiella effectors.

Public Health Relevance

Intracellular pathogens represent a serious threat to human health, and to devise strategies to combat infections by these microbes a more detailed understanding of how they modulate host cell function is needed. Thus, this project is focused on identifying molecular mechanisms that allow the intracellular pathogen Coxiella burnetii to regulate mammalian cell biology using novel bacterial proteins that manipulate the function of host proteins to enhance replication and survival.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
High Priority, Short Term Project Award (R56)
Project #
2R56AI064559-06A1
Application #
8785490
Study Section
Host Interactions with Bacterial Pathogens Study Section (HIBP)
Program Officer
Perdue, Samuel S
Project Start
2006-01-01
Project End
2014-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
6
Fiscal Year
2014
Total Cost
$374,625
Indirect Cost
$149,625
Name
Yale University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520