Extracellular Matrix Adhesins of Treponema pallidum

University Of Victoria, Victoria BC

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Abstract

Syphilis remains a public health threat worldwide, with an estimated 11 million new infections per year and a global burden of 36 million infections. Within the last decade there have been outbreaks of syphilis cases in major cities around the world, including within the United States, Canada, Europe, Australia and China. In 2019 the number of syphilis cases within the United States doubled over the previous five year period, while the number of congenital syphilis cases quadrupled ove r the same time period. Although syphilis is curable with penicillin treatment if diagnosed early, the worldwide syphilis prevalence shows that elimination of this disease will not occur through public health control measures alone, and instead willrequire development of effective strategies to prevent infection with this pathogen. Development of such infection prevention strategies requires an in depth knowledge of the pathogenic mechanisms used by this highly successful pathogen. The bacterium that causes syphilis, Treponema pallidum, is able to disseminate rapidly within the host during the early stages of infection to infect every organ and tissue. Minimal understanding exists surrounding the pathogenic mechanisms used by T. pal lidum to undergo widespread dissemination throughout the host, and gaining understanding within this highly relevant area of study will reveal novel approaches to disease prevention. The long-term objective of the current research project is to increase understanding of the pathogenic mechanisms used by T. pallidum to disseminate via the bloodstream and cause disease. To accomplish this objective, the following specific aims are proposed: (1) Determination of the host cell signaling pathways engaged by T. pallidum to facilitate treponemal dissemination across cell barriers, manipulation of host cell responses, and immune evasion; (2) Identification of T. pal lidum proteins responsible for manipulation of the host cell response; and (3) In vivo assessment of the role of the prioritized T. pallidum proteins in disease pathogenesis. These studies will increase understanding of the critical processes of T. pallidum dissemination and immune evasion. Further, they are expected to reveal novel pathogenic strategies for host cell signaling subversion and immune response alteration by T. pallidum which enables crossing of cellular barriers, accessing of deeper tissues within the host, and evasion of the immune response. RELEVANCE (See instructions): Syphilis infections continue to be prevalent worldwide, with an estimated global burden of 36 million cases and recent outbreaks observed in North America, Europe and Asia. The bacterium that causes syphilis is one of the most invasive organisms known, and this research investigates how the bacterium is able to spread so widely and rapidly within the host. This research will increase understanding of how the bacterium causes infection and will allow development of strategies to prevent syphilis infection. Program Director/Principal Investigator (Last, First, Middle): Cameron, Caroline Elizabeth