My laboratory studies the interaction of Borrelia burgdorferi, the agent of Lyme disease, with mammalian cells and tissues. This spirochete binds to members of a family of receptors on the surface of human cells termed "integrins", which are important in processes such as inflammation and blood vessel growth. Attachment to integrins probably contributes to the ability of B. burgdorferi to establish infection, and binding to multiple integrins is common to all infectious Borrelia tested. Understanding B. burgdorferi-integrin interaction is therefore key to understanding the development of Lyme disease. We used a filamentous phage display library to identify a B. burgdorferi protein that mediates bacterial binding to beta 3-chain integrins, and have defined portions of this protein that participate in integrin recognition. Our current work focuses on determining the role of Borrelia-integrin recognition in the course of infection and the development of Lyme disease in the mouse model. For this work, we are working toward generating B. burgdorferi mutants that either do not express the integrin ligand, or that express an altered form of the protein that does not bind integrins. We are also using the same phage library to identify Borrelia proteins that are involved in infection of specific tissues such as the joint and heart. Development of a promoter probe system for Borrelia is also under way. Our ultimate goal is to employ bacterial genetics (which is in a rudimentary state in Borrelia species) to identify new strategies to prevent or treat Lyme disease, and to identify mammalian molecules that are expressed specifically in the heart and joint and contribute to B. burgdorferi infection of these sites.

As mentioned above, we used a phage display library to identify a B. burgdorferi ligand for beta 3-chain integrins. Recent studies have demonstrated that expression of this protein is associated with the mammalian host, but not with the unfed tick vector. A new project in the lab is focusing on the mechanism of regulation of expression of this integrin ligand.

Additional work ongoing in the laboratory is aimed at the identification of a B. burgdorferi ligand for a non-beta 3-chain integrin, namely a5b1. For this work, we have taken advantage of the fact that the B. burgdorferi genome has been completely sequenced, and we have identified five candidates for further examination. In addition, selection for phage that bind alpha 5 beta 1 has been initiated.

A new project in the laboratory is following in the footsteps of our B. burgdorferi work to identify the adhesion mechanisms employed by another pathogenic spirochete, Leptospira interrogans. L. interrogans is an agent of leptospirosis, which affects humans and both wild and domesticated animals. Leptospirosis is thought to be the most prevalent zoonotic infection world-wide, but virtually nothing is known of how it causes infection and disease.

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