Project: Egress mechanisms of Coxiella burnetiiCopyright: © Lührmann
Coxiella burnetii is a Gram-negative, obligate intracellular pathogen and the causative agent of Q fever. The clinical presentation of the acute infection can vary from self-limiting flu-like illness to an atypical pneumonia or hepatitis. In rare cases chronic Q fever develops, with endocarditis as the most common manifestation.
Importantly, chronic Q fever is characterized by a high mortality rate, especially if treatment is delayed. Resident alveolar macrophages are the first target cells, but C. burnetii spread to other organs and cell types including endothelial cells. While we have information about the initial step of C. burnetii uptake and the maturation process of the C. burnetii-containing vacuole, it is completely unknown how C. burnetii spreads, i.e. how it exits its host cell to enter new target cells. Understanding this essential step during infection will be crucial to develop novel strategies to prevent C. burnetii spreading and, thus, disease.
Therefore, the aim of this proposal is to define the mechanism of egress of C. burnetii. We will image egress events using spinning disc microscopy to determine egress kinetics and to analyze the role of cell death in this process. To get insights into the role of C. burnetii genes and/or proteins during the egress process, we will investigate the role of the newly identified apoptosis-promoting T4SS effector proteins and of the genes shown to be up-regulated during later phases of infection.