Surface antigens of the syphilis spirochete and their potential as virulence determinants.
A unique physical feature of Treponema pallidum, the venereally transmitted agent of human syphilis, is that its outer membrane contains 100-fold less membrane-spanning protein than the outer membranes of typical gram-negative bacteria, a property that has been related to the chronicity of syphilitic infection. These membrane-spanning T. pallidum rare outer membrane proteins, termed TROMPs, represent potential surface-exposed virulence determinants and targets of host immunity. Only recently has the outer membrane of T. pallidum been isolated and its constituent 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. pallidum inner membrane protoplasmic cylinder complex, had been previously characterized lipoproteins and are, therefore, not membrane-spanning but rather membrane-anchored by their lipid moiety. In contrast, the 28-, 31-, and 65-kDa proteins are exclusively associated with the outer membrane. Both the purified native and an Escherichia coli recombinant outer membrane form of the 31-kDa protein, designated Tromp1, exhibit porin activity, thereby confirming the membrane-spanning outer membrane topology of Tromp1. The 28-kDa protein, designated Tromp2, has sequence characteristics in common with membrane-spanning outer membrane proteins and has also been recombinantly expressed in E. coli, where it targets exclusively to the E. coli outer membrane. The 65-kDa protein, designated Tromp3, is present in the least amount relative to Tromps1 and 2. Tromps 1, 2, and 3 were antigenic when tested with serum from infection and immune syphilitic rabbits and humans. These newly identified TROMPs provide a molecular foundation for the future study of syphilis pathogenesis and immunity.
Blanco
D R
DR
Dept. Microbiology and Immunology, UCLA School of Medicine 90095, USA. dblanco@microimmun.medsch.ucla.edu
Miller
J N
JN
Lovett
M A
MA
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000302:isolation & purification*; D000954:Antigens, Surface / Q000235:genetics / Q000302:isolation & purification*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D004926:Escherichia coli / Q000235:genetics; D005614:Freeze Fracturing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D008854:Microscopy, Electron; D018272:Porins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D013587:Syphilis / Q000209:etiology / Q000276:immunology; D014210:Treponema pallidum / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D014774:Virulence / Q000276:immunology
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D008565:Membrane Proteins; D018272:Porins; D011994:Recombinant Proteins; C093836:Tromp1 protein, Treponema pallidum; C104240:Tromp2 protein, Treponema pallidum