Grant: Cat Gr: STBBI Research in Canada: Beyond HIV/AIDS and Hepatitis C- Syphilis

Syphilis is a sexually transmitted infection causing severe, life-lasting health problems when untreated. It increases the risk of acquisition and transmission of HIV and harms unborn children when transmitted via the placenta during pregnancy. Worldwide, the incidence of syphilis has been rapidly rising. At the same time, global shortage of appropriate antibiotics has been hindering treatment of the existing syphilis cases. The proposed project will focus on the following challenges. (1) The current diagnostic tests that detect an active infection have low sensitivity in the early stages of syphilis (62-76%), delaying treatment and increasing chances of further transmission. (2) Vaccine and drug trials are slow due to the lack of suitable molecular tests indicative of an active infection in rabbits. To address these issues, we will develop novel, lipid-based tools for combating syphilis. Our preliminary data show that infection with the causative agent of syphilis, Treponema pallidum, leads to alteration of lipid homeostasis in the host. We, therefore, hypothesize that lipids are suitable biomarkers of syphilis. In this project, we aim to use mass spectrometry and molecular biology approaches to (1) Develop and validate a novel lipid-based diagnostic assay, LIST (LIpid Syphilis Test), using hundreds of defined serum samples from people with and without syphilis, (2) Improve the sensitivity and specificity of the existing diagnostic tests detecting anti-cardiolipin antibodies, and (3) Design a lipid-based tool for monitoring the course of infection in rabbits. Our team combines expertise in T. pallidum biology, mass spectrometry, rabbit model of syphilis, and clinical diagnostics, ensuring the feasibility of the proposed work. Novel lipid-based assays described in this proposal will aid in fast and efficient diagnostic methods and vaccine testing pipelines. These tools are essential for decreasing, and eventually eliminating, syphilis cases around the world.