After uptake into mammalian cells by microfilament-dependent endocytosis, C. burnetii remains in a membrane-bound vacuole. This C. burnetii-containing vacuole (CCV) initially appears to mature similarly to phagosomes containing avirulent bacteria, undergoing fusion with endosomes and lysosomes, resulting in the formation of a phagolysosomal compartment. However, C. burnetii delays the maturation of the CCV probably through interactions between the early CCV and the autophagic pathway. How C. burnetii mediates establishment of the phagolysosomal-like compartment in which it resides and replicates, is not well understood. However, a functional type IV secretion system (T4SS) is required, suggesting that bacterial effector proteins may directly influence biogenesis of the C. burnetii-occupied vacuole.
C. burnetii has been shown to inhibit host cell apoptosis. Apoptosis is a programmed cell death pathway that is crucial for immune system maintenance and removal of damaged or infected cells. It was demonstrated that C. burnetii infection inhibits the induction of the intrinsic cell death pathway by preventing cytochrome C release from mitochondria and consequently inhibiting caspase 3 activation. Another study showed that C. burnetii infection inhibited not only the intrinsic but also the extrinsic apoptosis pathway. While the mechanism(s) of C. burnetii-induced inhibition of host cell apoptosis is not well understood, it is clear that it depends on a functional T4SS.
1.) Analysis of the T4SS effector-induced inhibition of apoptosis
To determine the diverse mechanisms employed by Coxiella burnetii to prevent host cell apoptosis, we will analyze the function of Coxiella burnetii T4SS substrates that interfere with signaling through the intrinsic and extrinsic apoptotic pathways.
2.) Host and Pathogen Determinants of Resolution or Chronic Inflammation in Coxiella burnetii Infection
We aim to identify how host and pathogen determinants influence cell death, cytokine secretion, and intracellular signalling in Coxiella burnetii infection. Thus, by investigating both host and pathogen factors we aim to clarify how Coxiella burnetii infection resolves or develops into chronic inflammation. (For more information please see: https://www.sfb1181.forschung.fau.eu/)
3.) Q-GAPS – Q fever GermAn Interdisciplinary Programm for reSearch subproject 7
C. burnetii infects a variety of host species. The infection route as well as the disease severity seems to be species-specific. To gain insight into the reasons underlying these differences we will investigate the interaction of C. burnetii with cells form different host species. (For more information please see: http://www.q-gaps.de/)