These highly interactive laboratories focus on the pathogenesis of syphilis and the immune response of Treponema pallidum in humans and in animal models.

• Lukehart, Centurion, Van Voorhis - Our current major interest is the newly-identified polymorphic tpr gene family of T. pallidum. This gene family comprises 2% of the T. pallidum genome and is hypothesized to encode surface-exposed antigens that are important in syphilis pathogenesis, are major targets of the protective immune response, and are promising vaccine candidates. We are exploring the possibility that these genes confer antigenic variation in T. pallidum, thus permitting persistence of the organism in immunocompetent hosts.

• Lukehart, Van Voorhis - Studies to date have indicated that the protective immune response to Treponema pallidum is mediated by Th1-type CD4+ lymphocytes and infiltrating macrophages. Ongoing projects in the laboratory include the cloning and characterization of major T cell antigens of T. pallidum, including the above Tpr antigens, and investigation of cytokine induction by these antigens.

• Marra - Invasion of the central nervous system by T. pallidum occurs in the early weeks of infection. The laboratory is exploring the immunologic response to T. pallidum within the CNS; and the efficacy of recommended therapy for CNS syphilis in immunocompetent and HIV-infected patients.

• Cameron - Little is currently known about the pathogenic mechanisms used by T. pallidum to initiate infection, disseminate to distant sites, and establish chronic infection that can persist for decades. One main research focus within the treponemal laboratories is to characterize T. pallidum attachment to host cells, as this step is central to the initiation of infection and also critical to bacterial dissemination. Three T. pallidum adhesins have been identified that mediate attachment to host extracellular matrix components, and studies are underway to characterize these adhesins and determine their role in treponemal pathogenesis.

• Van Voorhis, Cameron - The laboratories are conducting post-genomic studies to complement the wealth of information generated by sequencing of the T. pallidum genome. In these studies, outer membrane proteins are predicted by computer analyses performed on the published genome sequence. These proteins are subsequently expressed in a heterologous system and their function and contribution to pathogenesis investigated by performing functional assays and proteomic analyses.