Released peptidoglycan fragments are a biomarker for early stages of syphilis

ABSTRACT. Syphilis is a sexually transmitted bacterial infection that has plagued human health for nearly five centuries. Over the past 30 years, syphilis cases have skyrocketed, world-wide. Unless the disease-causing agent— Treponema pallidum—is detected and the patient treated, a multi-system infection occurs which can lead to death. Current diagnostics are indirect tests that rely on a serological response, which takes weeks to develop. Furthermore, serology does not report on the status of infection, just exposure. New diagnostics that accurately detect the syphilis agent, early in disease, would greatly improve patient outcomes by providing immediate access to effective therapy. The development of new syphilis diagnostic tests has been stalled by several obstacles, namely the inability to culture T. pallidum in the lab. Recent advances in culture methods have led to our lab continuously propagating T. pallidum for more than a year and has precipitated several discoveries in spirochete biology. We have discovered that the bacterium that causes syphilis sheds large amounts of its peptidoglycan (PG) cell-wall into its environment as it grows. Virtually all bacteria possess PG, but, as it turns out, the PG of T. pallidum is extremely unique. These findings led us to hypothesize that the detection of shed T. pallidum PG fragments can act as a biomarker for all stages of the disease, including immediately after transmission. We have developed a recombinant, monoclonal antibody that is highly specific for released T. pallidum PG fragments. In this proposal, we will functionalize our monoclonal antibody to covalently attach a DNA aptamer and use this technology to create an Immuno-PCR diagnostic platform. Using experimental animal models, along with human patient samples, we will critically test the sensitivity and specificity of our novel system. If successful, our diagnostic tool will specifically detect infection hours after acquisition and, unlike serological tests, it will not be impacted by previous exposure. Together, our studies may change the way we diagnose syphilis.