J. Exp. Med., Volume 189, Number 4, February 15, 1999 647-656

Treponema pallidum Major Sheath Protein Homologue Tpr K Is a Target of Opsonic Antibody and the Protective Immune Response

By Arturo Centurion-Lara, Christa Castro, Lynn Barrett, Caroline Cameron, Maryam Mostowfi, Wesley C. Van Voorhis, and Sheila A. Lukehart

From the Department of Medicine, University of  Washington, Seattle, Washington 98195

We have identified a family of genes that code for targets for opsonic antibody and protective immunity in T. pallidum subspecies pallidum using two different approaches, subtraction hybridization and differential immunologic screening of a T. pallidum genomic library. Both approaches led to the identification of a polymorphic multicopy gene family with predicted amino acid homology to the major sheath protein of Treponema denticola. One of the members of this gene family, tpr K, codes for a protein that is predicted to have a cleavable signal peptide and be located in the outer membrane of the bacterium. Reverse transcription polymerase chain reaction analysis of T. pallidum reveals that Tpr K is preferentially transcribed in the Nichols strain of T. pallidum. Antibodies directed to purified recombinant variable domain of Tpr K can opsonize T. pallidum, Nichols strain, for phagocytosis, supporting the hypothesis that this portion of the protein is exposed at the surface of the treponeme. Immunization of rabbits with the purified recombinant variable domain of Tpr K provides significant protection against infection with the Nichols strain of T. pallidum. This gene family is hypothesized to be central to pathogenesis and immunity during syphilis infection.

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