Egress mechanisms of Coxiella burnetii

• Applicant: Professorin Dr. Anja Lührmann
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 446404050

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. In our preliminary experiments we observed at later stages of infection occasionally cell death of C. burnetii infected cells and release of bacteria. The released bacteria can infect new target cells without direct cell to cell contact and are capable of replicating. In addition we have identified C. burnetii type IV secretion system (T4SS) effector proteins with apoptosis-promoting activity, which might be involved in the egress mechanisms. Furthermore, we have performed RNAseq and identified bacterial genes which are upregulated at later stage of infection.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.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2225: Exit strategies of intracellular pathogens