Limits...
Treponema pallidum major sheath protein homologue Tpr K is a target of opsonic antibody and the protective immune response.

Centurion-Lara A, Castro C, Barrett L, Cameron C, Mostowfi M, Van Voorhis WC, Lukehart SA - J. Exp. Med. (1999)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Washington, Seattle, Washington 98195, USA. acentur@u.washington.edu

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

Intradermal challenge in a rabbit immunized with the recombinant Tpr K variable domain (A) and a normal unimmunized (B)  rabbit. The immunized rabbit was injected with 125 μg purified recombinant peptide in Ribi adjuvant (MPL + TDM + CWS), divided between intramuscular, intradermal, subcutaneous, and intraperitoneal sites,  and similarly boosted at 3 and 6 wk. The rabbits were challenged intradermally with 105 T. pallidum Nichols strain at each of eight sites 3 wk after  the final immunization. Black ink marks are seen to the left of the challenge sites.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2192927&req=5

Figure 5: Intradermal challenge in a rabbit immunized with the recombinant Tpr K variable domain (A) and a normal unimmunized (B) rabbit. The immunized rabbit was injected with 125 μg purified recombinant peptide in Ribi adjuvant (MPL + TDM + CWS), divided between intramuscular, intradermal, subcutaneous, and intraperitoneal sites, and similarly boosted at 3 and 6 wk. The rabbits were challenged intradermally with 105 T. pallidum Nichols strain at each of eight sites 3 wk after the final immunization. Black ink marks are seen to the left of the challenge sites.

Mentions: Be cause Tpr K induces opsonic antibody and because phagocytosis of opsonized bacteria by macrophages is thought to be a major clearance mechanism in syphilis, we investigated the ability of Tpr K to induce protection from challenge with T. pallidum, Nichols strain. Five immunized rabbits and five unimmunized controls were challenged intradermally with 105 per site at eight injection sites per animal. The lesions that appeared in Tpr K-immunized rabbits were atypical, in that they were flat and nonulcerative, and 95% were devoid of T. pallidum by darkfield microscopic examination of aspirates, and healed rapidly compared with control animals (Table III, Fig. 5). In contrast, the lesions that developed in the control rabbits developed large chancres, many of which (76%) progressed to ulceration and were positive for treponemes by darkfield microscopy. Parallel experiments revealed that immunization with unrelated recombinant molecules in adjuvant provided no protection, thus demonstrating that the level of protection induced by Tpr K variable domain is not due to an adjuvant effect (data not shown).


Treponema pallidum major sheath protein homologue Tpr K is a target of opsonic antibody and the protective immune response.

Centurion-Lara A, Castro C, Barrett L, Cameron C, Mostowfi M, Van Voorhis WC, Lukehart SA - J. Exp. Med. (1999)

Intradermal challenge in a rabbit immunized with the recombinant Tpr K variable domain (A) and a normal unimmunized (B)  rabbit. The immunized rabbit was injected with 125 μg purified recombinant peptide in Ribi adjuvant (MPL + TDM + CWS), divided between intramuscular, intradermal, subcutaneous, and intraperitoneal sites,  and similarly boosted at 3 and 6 wk. The rabbits were challenged intradermally with 105 T. pallidum Nichols strain at each of eight sites 3 wk after  the final immunization. Black ink marks are seen to the left of the challenge sites.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2192927&req=5

Figure 5: Intradermal challenge in a rabbit immunized with the recombinant Tpr K variable domain (A) and a normal unimmunized (B) rabbit. The immunized rabbit was injected with 125 μg purified recombinant peptide in Ribi adjuvant (MPL + TDM + CWS), divided between intramuscular, intradermal, subcutaneous, and intraperitoneal sites, and similarly boosted at 3 and 6 wk. The rabbits were challenged intradermally with 105 T. pallidum Nichols strain at each of eight sites 3 wk after the final immunization. Black ink marks are seen to the left of the challenge sites.
Mentions: Be cause Tpr K induces opsonic antibody and because phagocytosis of opsonized bacteria by macrophages is thought to be a major clearance mechanism in syphilis, we investigated the ability of Tpr K to induce protection from challenge with T. pallidum, Nichols strain. Five immunized rabbits and five unimmunized controls were challenged intradermally with 105 per site at eight injection sites per animal. The lesions that appeared in Tpr K-immunized rabbits were atypical, in that they were flat and nonulcerative, and 95% were devoid of T. pallidum by darkfield microscopic examination of aspirates, and healed rapidly compared with control animals (Table III, Fig. 5). In contrast, the lesions that developed in the control rabbits developed large chancres, many of which (76%) progressed to ulceration and were positive for treponemes by darkfield microscopy. Parallel experiments revealed that immunization with unrelated recombinant molecules in adjuvant provided no protection, thus demonstrating that the level of protection induced by Tpr K variable domain is not due to an adjuvant effect (data not shown).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Washington, Seattle, Washington 98195, USA. acentur@u.washington.edu

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus