Coxiella burnetii is a Gram negative bacterium that causes the zoonotic illness Q fever (for query fever). This disease can be life-threatening and ranges from an acute, flu-like illness to a chronic form of that frequently presents as endocarditis. Due to its high level of infectivity (a single organism may cause disease), its ability to be infectious when it is aerosolized, and its extreme resistance to harsh environmental conditions, C. burnetii displays the properties necessary for a potential biowarfare agent. A better understanding of how this organism causes disease should provide information on how to defend against its misuse. C. burnetii is an obligate intracellular pathogen that curiously replicates inside the hostile environment of a lysosome, a compartment that is normally exceedingly bactericidal. The factors that allow this organism to survive inside lysosomes, replicate inside host cells, and cause disease have not been identified. The major reason for this lack of progress is due to the fact that C. burnetii cannot be cultured in the absence of eukaryotic host cells, thereby limiting traditional genetic analysis. An alternative approach has been provided by the recent completion of the C. burnetii genome project. By examining the C. burnetii genome for possible virulence factors, it was discovered that it contains homologues to a secretion system used by the related pathogen Legionella pneumophila. Similar to C. burnetii, L. pneumophila replicates inside host cells although it begins its replicative cycle in a modified vacuole prior to fusing with lysosomes. L. pneumophila uses its specialized secretion system, encoded by the dot/icm genes, to export a number of virulence factors into macrophages in order to alter the endocytic pathway. Remarkably C. burnetii contains homologues to 23 of the 26 known L. pneumophila Dot/Icm proteins. We propose to determine if the C. burnetii Dot/Icm homologues are needed for this pathogen to replicate inside host cells and to identify proteins secreted by this system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI058083-01A1
Application #
6868317
Study Section
Special Emphasis Panel (ZRG1-IDM-A (90))
Program Officer
Perdue, Samuel S
Project Start
2005-03-01
Project End
2007-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
1
Fiscal Year
2005
Total Cost
$267,750
Indirect Cost
Name
Washington University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130