Treponema pallidum Lipoprotein TP0435 Expressed in Borrelia burgdorferi Produces Multiple Surface/Periplasmic Isoforms and mediates Adherence.

The ability of Treponema pallidum, the syphilis spirochete to colonize various tissues requires the presence of surface-exposed adhesins that have been difficult to identify due to the inability to culture and genetically manipulate T. pallidum. Using a Borrelia burgdorferi-based heterologous system and gain-in-function approach, we show for the first time that a highly immunogenic lipoprotein TP0435 can be differentially processed into multiple isoforms with one variant stochastically displayed on the spirochete surface. TP0435 was previously believed to be exclusively located in T. pallidum periplasm. Furthermore, non-adherent B. burgdorferi strain expressing TP0435 acquires the ability to bind to a variety of host cells including placental cells and exhibits slow opsonophagocytosis in vitro similar to poor ex vivo phagocytosis of T. pallidum by host macrophages reported previously. This phenomenon of production of both surface and periplasmic immunogenic lipoprotein isoforms has possible implications in immune evasion of the obligate pathogen T. pallidum during infection.