Vogel Lab Research
My laboratory is interested in how pathogens are able to survive and replicate inside host cells. We have chosen to focus on one bacterial pathogen, Legionella pneumophila, that is able to grow inside the hostile environment of professional phagocytic cells such as macrophages and fresh water amoebae. Growth of L. pneumophila inside alveolar macrophages of the human lung results in a potentially fatal form of pneumonia called Legionnaires’ disease. L. pneumophila is able to survive inside host cells by preventing fusion of the nascent phagosome with the degradative compartment, the lysosome.
We have discovered a large number of L. pneumophila genes that are absolutely required for intracellular replication. These genes are called “dot” for defect in organelle trafficking because mutant strains lacking these genes are unable to perturb the normal endocytic pathway of the macrophage. Based on similarities between the dot genes and bacterial conjugation systems, we believe that the dot machine constitutes an export apparatus that evolved from a plasmid transfer system. The dot secretion complex presumably is used to deposit virulence factor(s) into host cells that are then responsible for preventing phagosome-lysosome fusion. In addition to L. pneumophila, a number of other pathogens including Bordetella pertussis, Helicobacter pylori, and Brucella abortus contain related complexes which have all been classified as type IV secretion systems. Determining how these specialized export apparatuses function will allow us to understand how these pathogens cause disease and reveal methods to prevent or inhibit their action.