SURFACE-ANTIGENS OF THE SYPHILIS SPIROCHETE AND THEIR POTENTIAL AS VIRULENCE DETERMINANTS

A unique physical feature of Treponema pallidum, the venereally transm itted agent of human syphilis, is that its outer membrane contains 100 -fold less membrane-spanning protein than the outer membranes of typic al gram-negative bacteria, a property that has been related to the chr onicity of syphilitic infection. These membrane-spanning T. pallidum r are outer membrane proteins, termed TROMPs, represent potential surfac e-exposed virulence determinants and targets of host immunity. Only re cently has the outer membrane of T. pallidum been isolated and its con stituent proteins identified. Five proteins of molecular mass 17-, 28- , 31-, 45-, and 65-kDa were outer membrane associated. The 17- and 45- kDa proteins, which are also present in greater amounts with the T. pa llidum inner membrane protoplasmic cylinder complex, had been previous ly characterized lipoproteins and are, therefore, not membrane-spannin g but rather membrane-anchored by their lipid moiety. In contrast, the 28-, 31-, and 65-kDa proteins are exclusively associated with the out er membrane. Both the purified native and an Escherichia coli recombin ant outer membrane form of the 31-kDa protein, designated Tromp1, exhi bit porin activity, thereby confirming the membrane-spanning outer mem brane topology of Tromp1. The 28-kDa protein, designated Tromp2, has s equence characteristics in common with membrane-spanning outer membran e proteins and has also been recombinantly expressed in E. coli, where it targets exclusively to the E. coli outer membrane. The 65-kDa prot ein, designated Tromp3, is present in the least amount relative to Tro mps1 and 2. Tromps 1, 2, and 3 were antigenic when tested with serum f rom infection and immune syphilitic rabbits and humans. These newly id entified TROMPs provide a molecular foundation for the future study of syphilis pathogenesis and immunity.