Research in the Coburn laboratory focus on pathogenic spirochetes, a group of bacteria that are able to cause persistent, disseminated infections in immunocompetent animals, including humans. We are currently working with Borrelia burgdorferi, which is maintained in a tick-animal cycle in nature. We also work with another pathogenic spirochete, Leptospira interrogans. Leptospires are maintained in infected animals in nature, but can also survive in water and mud. Since both pathogens are maintained in animal reservoirs in nature, both are referred to as zoonotic infections. The focus of our work with both Borrelia and Leptospira is to identify and then test the biologic significance of bacterial proteins that help the bacteria bind to mammalian cell surface receptors, to identify the mammalian cell surface receptors recognized by the bacteria, and ultimately the biological and pathologic significance of the interaction between the bacterial protein and the mammalian receptor.
In the Borrelia work, we have two main projects ongoing in the lab. In one, we are trying to understand the mechanisms behind the requirement for the B. burgdorferi protein, P66, for the bacteria to cause infection in mammals. P66 binds to mammalian cell surface receptors called integrins and serves as a porin in the bacterial outer membrane. We know that the integrin binding function is important for the bacteria to cross the endothelial layers that line the vascular system and disseminate to different sites in the body. In another Borrelia project, we developed a new experimental model to determine the roles of bacterial adhesive proteins in how the bacteria interact with endothelial cells to colonize different tissues in mammals, and how they survive the mammalian defenses in the bloodstream.
In the Leptospira work, we also focus on how the bacteria interact with endothelial cells. In severe cases of leptospirosis, widespread endothelial damage is seen, and this is associated with hemorrhage. L. interrogans binds to an endothelial cell surface receptor called VE-cadherin, which helps the endothelial cells form cell-cell junctions that maintain the integrity of small blood vessels. We are currently determining how the bacteria disrupt cadherin-cadherin interactions, and determining whether the bacterial proteins that bind VE-cadherin are responsible for the endothelial disruption caused by the bacteria. In a second Leptospira project, we are working to identify the bacterial proteins that help the bacteria bind to the endothelial layer to promote bacterial association with the kidney, where the bacteria reside in a chronically infected animal and from where they are released into the environment.
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