Gene conversion: a mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection.
The tprK gene sequence of Treponema pallidum subspecies pallidum (T. pallidum) is heterogeneous within and among isolates. Heterogeneity in the tprK open reading frame is localized in seven discrete variable (V) regions, and variability results from apparent base changes, insertions or deletions. The TprK V regions are the focus of anti-TprK antibodies arising during infection. To test our hypothesis that V region sequences change during infection and passage, we developed a clonal isolate from the Chicago strain of T. pallidum and confirmed V region diversification during passage of this isolate. We describe the sequence anatomy of the seven V regions of tprK and the identification of putative donor sites for new V region sequences, and we propose a model for generation of new V regions by segmental gene conversion. These findings suggest that antigenic variation of TprK occurs in T. pallidum and may be important in immune evasion and persistence.
Centurion-Lara
Arturo
A
Department of Medicine, University of Washington, Harborview Medical Center, Box 359779, 325 Ninth Ave., Seattle, WA 98104, USA. acentur@u.washington.edu
LaFond
Rebecca E
RE
Hevner
Karin
K
Godornes
Charmie
C
Molini
Barbara J
BJ
Van Voorhis
Wesley C
WC
Lukehart
Sheila A
SA
D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D004269:DNA, Bacterial / Q000737:chemistry / Q000302:isolation & purification; D005785:Gene Conversion; D005798:Genes, Bacterial; D014644:Genetic Variation; D008297:Male; D008969:Molecular Sequence Data; D018272:Porins / Q000235:genetics* / Q000276:immunology*; D011817:Rabbits; D017422:Sequence Analysis, DNA; D013587:Syphilis / Q000382:microbiology*; D013737:Testis / Q000382:microbiology; D014210:Treponema pallidum / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity
D000954:Antigens, Surface; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D018272:Porins; C099361:major outer sheath protein, Treponema