Treponema Laboratories
University of Washington • Department of Medicine

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Treponemal research at the University of Washington and Harborview Medical Center id directed by three faculty researchers (Sheila Lukehart, Christina Marra, and Arturo Centurion-Lara), and is located in adjacent laboratories in the HMC R&T Building. 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 - 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 examining antigenic variation in one member of this family, TprK, including the molecular mechanism of variation, the consequences of TprK variation on immunological function in the host, and the host factors that influence sequence variation. A comparative study of the tpr family is being conducted with the goal of identifying key genetic differences among the subspecies and species of pathogenic Treponema, including the agents of yaws, bejel, and the rabbit pathogen Treponema paraluiscuniculi. The functions of identified genes will be explored to determine their effect on the pathogenesis of their respective diseases. Research Support: AI42143 and AI63940

Marra, Lukehart - Neurosyphilis and syphilis/AIDS interactions. Defining laboratory predictors of neurosyphilis, determining the efficacy of neurosyphilis treatment in HIV-coinfected individuals, development of new laboratory methods for establishment of a neurosyphilis diagnosis. Research Support: NS34235

Marra, Centurion-Lara, Lukehart - Molecular Typing. Identification and evaluation of molecular targets for development of a molecular typing method for T. pallidum transmission. This method will be applied to epidemiological studies of syphilis transmission and strain distribution.

Centurion-Lara - Gene Regulation in T. pallidum. Mechanisms of regulation of tpr gene expression, role of regulatory protiens (CRP), functions of sigma factors, etc. Research Support: UW Royalty Research Fund and AI42143

Lukehart - Vaccine Development. Studies are ongoing, in collaboroation with Dr. Caroline Cameron, University of Victoria, and the Wasington Vaccine Alliance, to develop and test and effective syphilis vaccine. Candidate antigens have been selected based upon their predicted cell surface location in T. pallidum, their sequence conservation among strains of T. pallidum, and their demonstrated protective capacity in pilot studies. Chimeric recombinant antigens, combining key immuogenic regions of the candidate antigens, are being studied. Research Support: LSDF WAVA

Lukehart - 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.

Lukehart - Mulitple collaborative studies exploring the geographical distribution of azithromycin resistance mutation in strains of T. pallidum. Identification of the genetic basis for the azithromycin-resistance phenotype.