DESCRIPTION (Adapted from applicant's application): Lyme disease, caused by infection with Borrelia burgdorferi, is the most common vector-borne disease in the United States. The mechanisms of pathogenesis are not well understood. Identification of bacterial factors involved in pathogenesis can be accomplished by comparing non-infectious variants of B. burgdorferi that arise during in vitro culture with wild-type infectious organisms. During previous studies high-infectivity and low- infectivity clonal populations of B. burgdorferi strain Sh2 were characterized. In specific aim 1, studies with these clonal populations will be employed to examine biological properties associated with infectivity, including cytadherence, invasiveness, susceptibility to phagocytosis, resistance to antibody killing and cytokine production. Specific aim 2 will involve the identification and characterization of genetic elements and gene products that are present in high-infectivity organisms but absent or underexpressed in low-infectivity B. burgdorferi. Specific aim 3 will examine the immunologic reactivity of any proteins found to be associated with infectivity. In specific aim 4, genetic transfer techniques will be developed in order to facilitate the transformation of low-infectivity organisms to high-infectivity phenotypes. The resulting information will potentially improve our understanding of the pathogenesis of Lyme disease and lead to improved diagnosis, treatment and prevention.