The Role of Coxiella Effector Proteins in Infection and Disease

Coxiella burnetii is an intracellular pathogen that causes the human disease Q-fever. This project is focused on the novel mechanisms Coxiella has evolved to manipulate the host cell. The Coxiella Dot/Icm type IVb secretion system is essential for intracellular replication. The goal of this project is to understand how effector proteins delivered into

host cells by the Dot/Icm system enable Coxiella to replicate in a hydrolytic lysosomal organelle and evade host detection. We have developed genetic tools to identify the important Coxiella proteins that are required for host manipulation. This project will leverage these genetic tools in combination with molecular and biochemical approaches

to investigate how these effector proteins interfere with host pathogen sensors, promote biogenesis of the unique Coxiella-containing vacuole (CCV), and facilitate infection in animals. Knowledge gained from these studies will lead to a greater understanding of pathogen adaptations that enable Coxiella to infect mammalian hosts and the immune

pathways that are important for controlling intracellular bacterial pathogens. Specific goals include functional analysis of the proteins EmcA and EmcB that are involved in suppression of host immune responses, using newly developed genetic tools to define epistatic interactions between effectors required for CCV biogenesis, and to use

bioluminescence imaging to measure virulence defects displayed by Coxiella effector mutants.