The Lukehart laboratory studies the pathogenesis of syphilis and the immune response to Treponema pallidum in humans and in animal models. Our current major interest is the 12-membered tpr gene family of T. pallidum, which is hypothesized to encode surface-exposed antigens that are major targets of the protective immune response, may be involved in immune evasion, and are promising vaccine candidates. We have demonstrated that one member of the Tpr family, TprK, undergoes antigenic variation; studies related to the immunological relevance and molecular mechanism of this variation are ongoing. New studies are focused on TprC and TprD, which are also surface exposed, and which differ in sequence among T. pallidum strains and subspecies. The laboratory is also working to identify surface molecules that are targets of opsonization and to define the kinetics of and requirements for bactericidal activity by macrophages. Many of the projects described above involve collaborations with Drs. Arturo Centurion-Lara and Lorenzo Giacani.
Additionally, our laboratory is involved in studies of clinical aspects of syphilis. With Dr. Christina Marra (Neurology), the laboratory is exploring the molecular basis for neuroinvasion, the immunologic response to T. pallidum within the CNS, and the efficacy of recommended therapy for CNS syphilis in immunocompetent and HIV-infected patients. Other ongoing studies involve the investigation of emerging macrolide resistance, application of a molecular typing method for T. pallidum to epidemiological studies of syphilis, and studies of yaws in Papua New Guinea..
Giacani L, Brandt SL, Puray-Chavez M, Brinck Reid T, Godornes C, Molini BJ, Benzler M, Hartig JS, Lukehart SA, Centurion-Lara A . Comparative Investigation of the Genomic Regions Involved in Antigenic Variation of the TprK Antigen among Treponemal Species, Subspecies, and Strains. J Bacteriol.194: 4208-25, 2012. PMC3416249.
Giacani L, Chattopadhyay S, Centurion-Lara A, Jeffrey BM, Le HT, Molini BJ, Lukehart SA, Sokurenko EV, Rockey DD. Footprint of positive selection in Treponema pallidum subsp. pallidum genome sequences suggests adaptive microevolution of the syphilis pathogen. PLoS Negl Trop Dis. 6(6):e1698, 2012. PMC3373638
Grimes M, Sahi SK, Godornes BC, Tantalo LC, Roberts N, Bostick D, Marra CM, Lukehart SA. Two Mutations associated with Macrolide Resistance in Treponema pallidum: Increasing Prevalence and Correlation with Molecular Strain Type in Seattle, Washington. Sex Trans Dis. 39:954-8, 2012. PMC3668457
Centurion-Lara A, Giacani L, Godornes C, Molini BJ, Brinck Reid T, Lukehart SA Fine Analysis of Genetic Diversity of the tpr Gene Family among Treponemal Species, Subspecies and Strains. PLoS Negl Trop Dis 7(5): e2222, 2013. PMC3656149
Mitja O,Lukehart SA, Pokowas G, Moses P, Kapa A, Paru R, Godornes C, Robson J, Cherian S, Houinei W, Kazadi W, Siba P, de Lazzari E, Bassat Q. Haemophilus ducreyi is major cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: A prospective cohort study. Lancet Glob Hlth 2: e235–241, 2014.