S07.5 Understanding Dissemination of Treponema Pallidum Within the Host - is There Hope For a Syphilis Vaccine?. (13th July 2013)

• Record Type: Journal Article
• Authors: Houston, S; Hof, R; Wetherell, C; Phillips, A; Denchev, Y; Cameron, C E
• Is Part Of: Sexually transmitted infections. Volume 89(2013)Supplement 1
• Page Start: A14
• Page End: A14
• Publication Date: 2013-07-13
• Subjects: protease -- Syphilis -- Vaccine; Sexually transmitted diseases -- Periodicals; HIV infections -- Periodicals; 616.951005
• DOI: 10.1136/sextrans-2013-051184.0042
• Languages: English
• ISSNs: 1368-4973

Abstract

Abstract : Treponema pallidum is a highly invasive spirochete that disseminates to organ sites distal to the site of primary infection and is able to cross both the blood-brain and placental barriers during the course of infection. The corkscrew motility used by T. pallidum undoubtedly contributes to its invasive nature. However, this signature motility is shared with other spirochetes and thus the factors responsible for the widespread dissemination capability that is unique to T. pallidum remain unknown. We have identified the treponemal-specific, surface-localised protein pallilysin as a dual functioning adhesin/metalloprotease that exhibits specific attachment to, and degradation of, multiple extracellular matrix components. Pallilysin is produced as an inactive proprotease that can be activated via either autocatalytic cleavage or host-originating thrombin cleavage. Purified recombinant pallilysin, as well as a non-invasive model treponeme heterologously expressing pallilysin on its surface, exhibit specific degradation of fibrin clots. Pallilysin immunisation alters the course of T. pallidum dissemination following challenge within the rabbit model of syphilis infection, with immunised rabbits exhibiting a reduced bacterial burden within organs distal to the site of challenge compared to unimmunized control rabbits. Further, rabbit infectivity tests (RIT) showed that rabbits receiving lymph nodes from challenged, unimmunized rabbits seroconverted and developed orchitis by 30 days post-transfer, while 66% of RIT rabbits receiving lymph nodes from challenged, pallilysin-immunised rabbits remained seronegative and had no signs of orchitis at the termination of the experiment (day 185 post-transfer). Collectively these studies identify pallilysin as a T. pallidum -specific metalloprotease that (1) exploits the host coagulation cascade to facilitate protease activation, (2) plays a central role in treponemal dissemination and (3) shows promise as a novel syphilis vaccine candidate.