Coxiella burnetii, the causative agent of Q fever, is an obligate intracellular bacterium capable of replicating within acidic phagolysosomes of host cells. A Type IV secretion system, homologous to the Dot/lcm system found in Legionella pneumophila and a family of putative translocated proteins containing ankyrin repeat domains (Ank proteins) have recently been identified in Coxiella. Preliminary data demonstrate that some of the Coxiella Ank proteins are efficiently translocated by the Legionella Dot/lcm system into the host cell. We hypothesize that these proteins function to modulate host cell processes in order to create a suitable environment for Coxiella replication and intracellular survival. Using immuno-fluorescence microscopy, we will determine the localization of endogenously-produced Ank proteins in host cells infected with Coxiella. Ectopic expression of the Ank proteins in eukaryotic host cells will reveal host processes that are affected by the Ank proteins. As ankyrin repeat domains function in protein-protein interactions, genetic and biochemical approaches will be used to identify interacting host cell proteins in an attempt to address the role(s) of the Ank proteins in Coxiella pathogenesis. ? ? ?
| Carey, Kimberly L; Newton, Hayley J; Luhrmann, Anja et al. (2011) The Coxiella burnetii Dot/Icm system delivers a unique repertoire of type IV effectors into host cells and is required for intracellular replication. PLoS Pathog 7:e1002056 |
| Lührmann, Anja; Nogueira, Catarina V; Carey, Kimberly L et al. (2010) Inhibition of pathogen-induced apoptosis by a Coxiella burnetii type IV effector protein. Proc Natl Acad Sci U S A 107:18997-9001 |
