When microorganisms enter the sterile section of our body (e.g., after trauma), they readily encounter professional phagocytic cells (in particular, neutrophils and macrophages) which ingest and kill the microbes. Some intracellular pathogens, however, escape this host defense mechanism and can even multiply in phagocytic host cells. These microorganisms include members of the species Rhodococcus equi which are found in macrophage phagosomes that do not mature to phagolysosomes, and which can destroy their host cells in a matter of hours to days. These two unusual features are uniquely regulated by the presence of a plasmid which is essential for virulence of R. equi in mice and horses. The proposed studies will contribute to an understanding at the molecular level of how Rhodococcus-containing phagosomes are compartmentalized during an infection, how the bacteria can destroy their host cells and to what extent intracellular compartmentalization determines host cell destruction.
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