title: Antigenic variation in Treponema pallidum: TprK sequence diversity accumulates in response to immune pressure during experimental syphilis.
abstract: Pathogens that cause chronic infections often employ antigenic variation to evade the immune response and persist in the host. In Treponema pallidum (T. pallidum), the causative agent of syphilis, the TprK Ag undergoes variation of seven V regions (V1-V7) by nonreciprocal recombination of silent donor cassettes with the tprK expression site. These V regions are the targets of the host humoral immune response during experimental infection. The present study addresses the causal role of the acquired immune response in the selection of TprK variants in two ways: 1) by investigating TprK variants arising in immunocompetent versus immunosuppressed hosts; and 2) by investigating the effect of prior specific immunization on selection of TprK variants during infection. V region diversity, particularly in V6, accumulates more rapidly in immunocompetent rabbits than in pharmacologically immunosuppressed rabbits (treated with weekly injections of methylprednisolone acetate). In a complementary experiment, rabbits preimmunized with V6 region synthetic peptides had more rapid accumulation of V6 variant treponemes than control rabbits. These studies demonstrate that the host immune response selects against specific TprK epitopes expressed on T. pallidum, resulting in immune selection of new TprK variants during infection, confirming a role for antigenic variation in syphilis.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98104, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Giacani
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Molini
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Kim
authors.forename: B Charmie
authors.initials: BC
authors.lastname: Godornes
authors.forename: B Troy
authors.initials: BT
authors.lastname: Leader
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Tantalo
authors.forename: Arturo
authors.initials: A
authors.lastname: Centurion-Lara
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Lukehart
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000940:Antigenic Variation / Q000235:genetics* / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D004195:Disease Models, Animal; D008969:Molecular Sequence Data; D018272:Porins / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013587:Syphilis / Q000235:genetics* / Q000276:immunology; D014210:Treponema pallidum / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018272:Porins; D012333:RNA, Messenger; C099361:major outer sheath protein, Treponema