Variable major proteins of Borrelia hermsii. Epitope mapping and partial sequence analysis of CNBr peptides.

Barstad, Paul A.; Coligan, John E.; Raum, Michael G.; Barbour, Alan G.

doi:10.1084/jem.161.6.1302

Cited by 84 publications

(67 citation statements)

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“…A major surfaceexposed lipoprotein designated the variable membrane protein (Vmp) has been correlated with this antigenic variation (4, 9, 11). This switching from an initial Vmp type to another prior to the establishment of a protective antibody response is thought to enable the escape of these organisms from antibody-mediated opsonization and complement killing.Although the molecular basis of antigenic variation has been thoroughly described by 8,9,11,18,25,33,40,[44][45][46], relatively little is known about other aspects of pathogenesis and immunity. B. hermsii, like other pathogenic spirochetes, has been shown by freeze fracture electron microscopy to have an extreme low density of outer membrane-spanning proteins (400 particles/mm 2 ) (63), like that for Treponema pallidum subsp.…”

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confidence: 99%

Sequence analysis and characterization of a 40-kilodalton Borrelia hermsii glycerophosphodiester phosphodiesterase homolog

Shang¹,

Skare²,

Erdjument‐Bromage³

et al. 1997

J Bacteriol

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We report the purification, molecular cloning, and characterization of a 40-kDa glycerophosphodiester phosphodiesterase homolog from Borrelia hermsii. The 40-kDa protein was solubilized from whole organisms with 0.1% Triton X-100, phase partitioned into the Triton X-114 detergent phase, and purified by fastperformance liquid chromatography (FPLC). The gene encoding the 40-kDa protein was cloned from a B. hermsii chromosomal DNA lambda EXlox expression library and identified by using affinity antibodies generated against the purified native protein. The deduced amino acid sequence included a 20-amino-acid signal peptide encoding a putative leader peptidase II cleavage site, indicating that the 40-kDa protein was a lipoprotein. Based on significant homology (31 to 52% identity) of the 40-kDa protein to glycerophosphodiester phosphodiesterases of Escherichia coli (GlpQ), Bacillus subtilis (GlpQ), and Haemophilus influenzae (Hpd; protein D), we have designated this B. hermsii 40-kDa lipoprotein a glycerophosphodiester phosphodiesterase (Gpd) homolog, the first B. hermsii lipoprotein to have a putative functional assignment. A nonlipidated form of the Gpd homolog was overproduced as a fusion protein in E. coli BL21(DE3)(pLysE) and was used to immunize rabbits to generate specific antiserum. Immunoblot analysis with anti-Gpd serum recognized recombinant H. influenzae protein D, and conversely, antiserum to H. influenzae protein D recognized recombinant B. hermsii Gpd (rGpd), indicating antigenic conservation between these proteins. Antiserum to rGpd also identified native Gpd as a constituent of purified outer membrane vesicles prepared from B. hermsii. Screening of other pathogenic spirochetes with anti-rGpd serum revealed the presence of antigenically related proteins in Borrelia burgdorferi, Treponema pallidum, and Leptospira kirschneri. Further sequence analysis both upstream and downstream of the Gpd homolog showed additional homologs of glycerol metabolism, including a glycerol-3-phosphate transporter (GlpT), a glycerol-3-phosphate dehydrogenase (GlpD), and a thioredoxin reductase (TrxB).The pathogenic spirochete Borrelia hermsii is one of the etiologic agents of tick-borne relapsing fever. Infection in humans and other vertebrates is commonly characterized by recurring episodes of high fever and bacteremia with intermittent afebrile periods (55). In humans, other clinical manifestations may include pronounced muscle and joint pains, splenomegaly, hepatomegaly, jaundice, and rash, as well as respiratory, cardiovascular, and central nervous system involvement (7). The well-documented relapse phenomenon is associated with the ability of these organisms to undergo multiphasic antigenic variation during the course of disease (56). A major surfaceexposed lipoprotein designated the variable membrane protein (Vmp) has been correlated with this antigenic variation (4, 9, 11). This switching from an initial Vmp type to another prior to the establishment of a protective antibody response is thought to enable the escape of...

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confidence: 99%

Sequence analysis and characterization of a 40-kilodalton Borrelia hermsii glycerophosphodiester phosphodiesterase homolog

Shang¹,

Skare²,

Erdjument‐Bromage³

et al. 1997

J Bacteriol

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“…The C-terminal invariable domain is also immunodominant, at least in mice as shown in the present study. In contrast, the conserved portions of other variable antigens including VSG and Vmp have never been found to be antigenic in a natural infection, although they may induce an antibody response by immunization in the presence of adjuvant (3,5,11). Their variable domains, in contrast, are highly immunogenic and serve as the major target of host protective antibodies (9,10,33).…”

Section: Vlse Is An Immunodominant Surface Antigen Of B Burgdorferi mentioning

confidence: 97%

“…It is well accepted that antigenic variation plays an essential role in the pathogenesis of African trypanosomiasis, relapsing fever, and cyclic rickettsemia, as immune evasion permits the establishment of chronic infection and disease (5,9,28,33,35). Initial data indicate that antigenic variation in B. burgdorferi also may be a factor in the pathogenesis of Lyme disease (36).…”

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confidence: 94%

“…Like other vector-borne pathogens, such as the protozoan Trypanosoma brucei (9,35), the spirochete Borrelia hermsii (5,33) and the ehrlichia Anaplasma marginale (28), the Lyme disease spirochete, Borrelia burgdorferi, expresses a surface antigen that undergoes antigenic variation (36). It is well accepted that antigenic variation plays an essential role in the pathogenesis of African trypanosomiasis, relapsing fever, and cyclic rickettsemia, as immune evasion permits the establishment of chronic infection and disease (5,9,28,33,35).…”

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confidence: 99%

“…In antigens such as the variant surface glycoprotein (VSG) of T. brucei (9,35) and the variable major protein (Vmp) of B. hermsii (5,33), variable portions encompass almost 70% of the primary sequences. In contrast, in VlsE, the variable surface antigen of B. burgdorferi, it is the invariable portions that account for more than 70% of the entire length of this antigen's primary sequence (19,36).…”

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C-Terminal Invariable Domain of VlsE May Not Serve as Target for Protective Immune Response againstBorrelia burgdorferi

2001

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VlsE, the variable surface antigen of the Lyme disease spirochete, Borrelia burgdorferi, contains two invariable domains, at the amino and carboxyl termini, respectively, which collectively account for approximately one-half of the entire molecule's length and remain unchanged during antigenic variation. It is not known if these two invariable domains are exposed at the surface of either the antigen or the spirochete. If they are exposed at the spirochete's surface, they may elicit a protective immune response against B. burgdorferi and serve as vaccine candidates. In this study, a 51-mer synthetic peptide that reproduced the entire sequence of the C-terminal invariable domain of VlsE was conjugated to the carrier keyhole limpet hemocyanin and used to immunize mice. Generated mouse antibody was able to immunoprecipitate native VlsE extracted from cultured B. burgdorferi B31 spirochetes, indicating that the C-terminal invariable domain was exposed at the antigen's surface. However, this domain was inaccessible to antibody binding at the surface of cultured intact spirochetes, as demonstrated by both an immunofluorescence experiment and an in vitro killing assay. Mouse antibody to the C-terminal invariable domain was not able to confer protection against B. burgdorferi infection, indicating that this domain was unlikely exposed at the spirochete's surface in vivo. We concluded that the C-terminal invariable domain was exposed at the antigen's surface but not at the surface of either cultured or in vivo spirochetes and thus cannot elicit protection against B. burgdorferi infection.

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Molecular mimicry and lyme borreliosis: A shared antigenic determinant between Borrelia burgdorferi and human tissue

Aberer

Brunner

Suchanek

et al. 1989

Annals of Neurology

119

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The pathogenesis of chronic manifestations in Lyme borreliosis, a disease induced by Borrelia burgdorferi, is at present unresolved. By testing monoclonal antibodies directed against various borrelia antigens, we found an antigenic determinant shared by the 41 kDa flagella protein and human tissue, especially prominent on myelinated fibers of human peripheral nerve, on nerve cells and axons of the central nervous system, as well as on certain epithelial cells (including joint synovia) and on heart muscle cells. Immune reactions against such a shared antigen could play a pathogenetic role in chronic organ manifestations of Lyme borreliosis.

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Variable major proteins of Borrelia hermsii. Epitope mapping and partial sequence analysis of CNBr peptides.

Cited by 84 publications

References 20 publications

Sequence analysis and characterization of a 40-kilodalton Borrelia hermsii glycerophosphodiester phosphodiesterase homolog

Sequence analysis and characterization of a 40-kilodalton Borrelia hermsii glycerophosphodiester phosphodiesterase homolog

C-Terminal Invariable Domain of VlsE May Not Serve as Target for Protective Immune Response againstBorrelia burgdorferi

Molecular mimicry and lyme borreliosis: A shared antigenic determinant between Borrelia burgdorferi and human tissue

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