Document Type



Spotted fever group (SFG) Rickettsia are obligate intracellular bacteria that are transmitted by ticks during a bloodmeal to a mammalian host. Interestingly, the SFG pathogen, Rickettsia conorii, has been shown to infect and grow in macrophages with a similar efficiency as the target endothelial cell, whereas a non-human pathogenic counterpart, Rickettsia montanensis, is unable to grow within macrophages. We have since determine that this phenotype applies to other pathogenic and non-human pathogenic Rickettsia, showing a correlation with growth in macrophages and rickettsial virulence. Recently, our lab has also defined host proteins that are altered during macrophage infection with R. conorii compared to R. montanensis to define alterations in host processes that may be essential for pathogen survival and replication. Among the proteins altered during macrophage infection with R. conorii are those involved in lipid metabolism. Therefore, we hypothesize that if pathogenic Rickettsia species, such as R. conorii, require host lipid metabolic processes, then inhibition of these pathways will negatively impact rickettsial survival and host modulation during infection of macrophages. Here, the requirement of central processes important for lipid metabolism, such as lipid droplet modification and catabolism, and fatty acid β-oxidation, for R. conorii survival in macrophages was elucidated. Conversely, a common way bacteria manipulate the host is through employment of effector proteins that are able to interact with host proteins to drive processes favorable for efficient bacterial infection. Herein we develop tools required for investigation of a putative Rickettsia rickettsii effector protein, RARP3. In summary, the findings presented within this thesis are necessary for further understanding the mammalian host:pathogen interaction in hopes to develop alternative therapeutics against spotted fever group Rickettsia.



Committee Chair

Martinez, Juan J.