Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1993 May;61(5):2182–2191. doi: 10.1128/iai.61.5.2182-2191.1993

Immunological and molecular polymorphisms of OspC, an immunodominant major outer surface protein of Borrelia burgdorferi.

B Wilske 1, V Preac-Mursic 1, S Jauris 1, A Hofmann 1, I Pradel 1, E Soutschek 1, E Schwab 1, G Will 1, G Wanner 1
PMCID: PMC280819  PMID: 8478108

Abstract

The gene of the immunodominant major protein pC of Borrelia burgdorferi was previously cloned and sequenced (R. Fuchs, S. Jauris, F. Lottspeich, V. Preac-Mursic, B. Wilske, and E. Soutschek, Mol. Microbiol. 6:503-509, 1992). pC is abundantly expressed on the outer surface of B. burgdorferi, as demonstrated by immunoelectron microscopy with monoclonal antibody L22 1F8. Accordingly, pC is renamed OspC, by analogy to the outer surface proteins OspA and OspB. Western immunoblot analysis of 45 B. burgdorferi isolates with monoclonal antibodies revealed that OspC is immunologically heterogeneous. Partial sequence analysis of the ospC gene confirmed the protein heterogeneity at the genetic level. We found that the degree of identity between the ospC partial sequences of five strains representing different OspA serotypes was only 63.3 to 85.4%. Immunological heterogeneity was also observed among representatives of the three newly designated genospecies of B. burgdorferi sensu lato, B. burgdorferi sensu stricto, B. garinii, and group VS461. Heterogeneity was confirmed for B. garinii at the genetic level. The ospC gene was also cloned from strains that did not express OspC, and antibody-reactive OspC was expressed in Escherichia coli. In addition, OspC-expressing variants were obtained from a nonexpressing strain by plating single colonies on solid medium. These findings confirm that the ospC gene is also present in nonexpressing strains. Because OspC is an immunodominant protein for the early immune response in Lyme borreliosis and was effective as a vaccine in an animal model, the immunological and molecular polymorphisms of ospC and OspC have important implications for the development of diagnostic reagents and vaccines.

Full text

PDF
2182

Images in this article

2186Image
on p.2186
2187Image
on p.2187
2187Image
on p.2187
2189Image
on p.2189
2189Image
on p.2189
2189Image
on p.2189

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adam T., Gassmann G. S., Rasiah C., Göbel U. B. Phenotypic and genotypic analysis of Borrelia burgdorferi isolates from various sources. Infect Immun. 1991 Aug;59(8):2579–2585. doi: 10.1128/iai.59.8.2579-2585.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson J. F., Magnarelli L. A., LeFebvre R. B., Andreadis T. G., McAninch J. B., Perng G. C., Johnson R. C. Antigenically variable Borrelia burgdorferi isolated from cottontail rabbits and Ixodes dentatus in rural and urban areas. J Clin Microbiol. 1989 Jan;27(1):13–20. doi: 10.1128/jcm.27.1.13-20.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anderson J. F., Magnarelli L. A., McAninch J. B. New Borrelia burgdorferi antigenic variant isolated from Ixodes dammini from upstate New York. J Clin Microbiol. 1988 Oct;26(10):2209–2212. doi: 10.1128/jcm.26.10.2209-2212.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baranton G., Postic D., Saint Girons I., Boerlin P., Piffaretti J. C., Assous M., Grimont P. A. Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461 associated with Lyme borreliosis. Int J Syst Bacteriol. 1992 Jul;42(3):378–383. doi: 10.1099/00207713-42-3-378. [DOI] [PubMed] [Google Scholar]
  5. Barbour A. G., Burgdorfer W., Grunwaldt E., Steere A. C. Antibodies of patients with Lyme disease to components of the Ixodes dammini spirochete. J Clin Invest. 1983 Aug;72(2):504–515. doi: 10.1172/JCI110998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barbour A. G., Heiland R. A., Howe T. R. Heterogeneity of major proteins in Lyme disease borreliae: a molecular analysis of North American and European isolates. J Infect Dis. 1985 Sep;152(3):478–484. doi: 10.1093/infdis/152.3.478. [DOI] [PubMed] [Google Scholar]
  7. Barbour A. G., Schrumpf M. E. Polymorphisms of major surface proteins of Borrelia burgdorferi. Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):83–91. doi: 10.1016/s0176-6724(86)80107-9. [DOI] [PubMed] [Google Scholar]
  8. Barbour A. G., Tessier S. L., Hayes S. F. Variation in a major surface protein of Lyme disease spirochetes. Infect Immun. 1984 Jul;45(1):94–100. doi: 10.1128/iai.45.1.94-100.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Barbour A. G., Tessier S. L., Stoenner H. G. Variable major proteins of Borrellia hermsii. J Exp Med. 1982 Nov 1;156(5):1312–1324. doi: 10.1084/jem.156.5.1312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Barbour A. G., Tessier S. L., Todd W. J. Lyme disease spirochetes and ixodid tick spirochetes share a common surface antigenic determinant defined by a monoclonal antibody. Infect Immun. 1983 Aug;41(2):795–804. doi: 10.1128/iai.41.2.795-804.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Barstad P. A., Coligan J. E., Raum M. G., Barbour A. G. Variable major proteins of Borrelia hermsii. Epitope mapping and partial sequence analysis of CNBr peptides. J Exp Med. 1985 Jun 1;161(6):1302–1314. doi: 10.1084/jem.161.6.1302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bergström S., Bundoc V. G., Barbour A. G. Molecular analysis of linear plasmid-encoded major surface proteins, OspA and OspB, of the Lyme disease spirochaete Borrelia burgdorferi. Mol Microbiol. 1989 Apr;3(4):479–486. doi: 10.1111/j.1365-2958.1989.tb00194.x. [DOI] [PubMed] [Google Scholar]
  13. Bissett M. L., Hill W. Characterization of Borrelia burgdorferi strains isolated from Ixodes pacificus ticks in California. J Clin Microbiol. 1987 Dec;25(12):2296–2301. doi: 10.1128/jcm.25.12.2296-2301.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Brandt M. E., Riley B. S., Radolf J. D., Norgard M. V. Immunogenic integral membrane proteins of Borrelia burgdorferi are lipoproteins. Infect Immun. 1990 Apr;58(4):983–991. doi: 10.1128/iai.58.4.983-991.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Brown R. N., Lane R. S. Lyme disease in California: a novel enzootic transmission cycle of Borrelia burgdorferi. Science. 1992 Jun 5;256(5062):1439–1442. doi: 10.1126/science.1604318. [DOI] [PubMed] [Google Scholar]
  16. Bundoc V. G., Barbour A. G. Clonal polymorphisms of outer membrane protein OspB of Borrelia burgdorferi. Infect Immun. 1989 Sep;57(9):2733–2741. doi: 10.1128/iai.57.9.2733-2741.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Burgdorfer W., Barbour A. G., Hayes S. F., Benach J. L., Grunwaldt E., Davis J. P. Lyme disease-a tick-borne spirochetosis? Science. 1982 Jun 18;216(4552):1317–1319. doi: 10.1126/science.7043737. [DOI] [PubMed] [Google Scholar]
  18. Daschner F. Emergence of resistance during selective decontamination of the digestive tract. Eur J Clin Microbiol Infect Dis. 1992 Jan;11(1):1–3. doi: 10.1007/BF01971262. [DOI] [PubMed] [Google Scholar]
  19. Dressler F., Whalen J. A., Reinhardt B. N., Steere A. C. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis. 1993 Feb;167(2):392–400. doi: 10.1093/infdis/167.2.392. [DOI] [PubMed] [Google Scholar]
  20. Fikrig E., Barthold S. W., Kantor F. S., Flavell R. A. Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. Science. 1990 Oct 26;250(4980):553–556. doi: 10.1126/science.2237407. [DOI] [PubMed] [Google Scholar]
  21. Fikrig E., Barthold S. W., Persing D. H., Sun X., Kantor F. S., Flavell R. A. Borrelia burgdorferi strain 25015: characterization of outer surface protein A and vaccination against infection. J Immunol. 1992 Apr 1;148(7):2256–2260. [PubMed] [Google Scholar]
  22. Fuchs R., Jauris S., Lottspeich F., Preac-Mursic V., Wilske B., Soutschek E. Molecular analysis and expression of a Borrelia burgdorferi gene encoding a 22 kDa protein (pC) in Escherichia coli. Mol Microbiol. 1992 Feb;6(4):503–509. doi: 10.1111/j.1365-2958.1992.tb01495.x. [DOI] [PubMed] [Google Scholar]
  23. Fuchs R., Wilske B., Preac-Mursic V., Schierz G. Purification of the Borrelia burgdorferi flagellum by use of a monoclonal antibody. Mol Cell Probes. 1990 Dec;4(6):451–462. doi: 10.1016/0890-8508(90)90004-j. [DOI] [PubMed] [Google Scholar]
  24. Grellner W., Erbguth F., Brade V. Serodiagnostik bei Lyme-Borreliose: Antikörpertiter und -spezifität im IFT und Western-Blot. Immun Infekt. 1989 Dec;17(6):189–194. [PubMed] [Google Scholar]
  25. Hu C. M., Gern L., Aeschlimann A. Changes in the protein profile and antigenicity of different Borrelia burgdorferi strains after reintroduction to Ixodes ricinus ticks. Parasite Immunol. 1992 Jul;14(4):415–427. doi: 10.1111/j.1365-3024.1992.tb00016.x. [DOI] [PubMed] [Google Scholar]
  26. Jonsson M., Noppa L., Barbour A. G., Bergström S. Heterogeneity of outer membrane proteins in Borrelia burgdorferi: comparison of osp operons of three isolates of different geographic origins. Infect Immun. 1992 May;60(5):1845–1853. doi: 10.1128/iai.60.5.1845-1853.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Karlsson M. Western immunoblot and flagellum enzyme-linked immunosorbent assay for serodiagnosis of Lyme borreliosis. J Clin Microbiol. 1990 Sep;28(9):2148–2150. doi: 10.1128/jcm.28.9.2148-2150.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kurashige S., Bissett M., Oshiro L. Characterization of a tick isolate of Borrelia burgdorferi that possesses a major low-molecular-weight surface protein. J Clin Microbiol. 1990 Jun;28(6):1362–1366. doi: 10.1128/jcm.28.6.1362-1366.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lane R. S., Pascocello J. A. Antigenic characteristics of Borrelia burgdorferi isolates from ixodid ticks in California. J Clin Microbiol. 1989 Oct;27(10):2344–2349. doi: 10.1128/jcm.27.10.2344-2349.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Luft B. J., Jiang W., Munoz P., Dattwyler R. J., Gorevic P. D. Biochemical and immunological characterization of the surface proteins of Borrelia burgdorferi. Infect Immun. 1989 Nov;57(11):3637–3645. doi: 10.1128/iai.57.11.3637-3645.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mursic V. P., Wilske B., Schierz G., Holmburger M., Süss E. In vitro and in vivo susceptibility of Borrelia burgdorferi. Eur J Clin Microbiol. 1987 Aug;6(4):424–426. doi: 10.1007/BF02013102. [DOI] [PubMed] [Google Scholar]
  32. Park H. K., Jones B. E., Barbour A. G. Erythema chronicum migrans of Lyme disease: diagnosis by monoclonal antibodies. J Am Acad Dermatol. 1986 Aug;15(2 Pt 2):406–410. doi: 10.1016/s0190-9622(86)70190-4. [DOI] [PubMed] [Google Scholar]
  33. Preac-Mursic V., Wilske B., Patsouris E., Jauris S., Will G., Soutschek E., Rainhardt S., Lehnert G., Klockmann U., Mehraein P. Active immunization with pC protein of Borrelia burgdorferi protects gerbils against B. burgdorferi infection. Infection. 1992 Nov-Dec;20(6):342–349. doi: 10.1007/BF01710681. [DOI] [PubMed] [Google Scholar]
  34. Preac-Mursic V., Wilske B., Reinhardt S. Culture of Borrelia burgdorferi on six solid media. Eur J Clin Microbiol Infect Dis. 1991 Dec;10(12):1076–1079. doi: 10.1007/BF01984935. [DOI] [PubMed] [Google Scholar]
  35. Sadziene A., Wilske B., Ferdows M. S., Barbour A. G. The cryptic ospC gene of Borrelia burgdorferi B31 is located on a circular plasmid. Infect Immun. 1993 May;61(5):2192–2195. doi: 10.1128/iai.61.5.2192-2195.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schaible U. E., Kramer M. D., Eichmann K., Modolell M., Museteanu C., Simon M. M. Monoclonal antibodies specific for the outer surface protein A (OspA) of Borrelia burgdorferi prevent Lyme borreliosis in severe combined immunodeficiency (scid) mice. Proc Natl Acad Sci U S A. 1990 May;87(10):3768–3772. doi: 10.1073/pnas.87.10.3768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schwan T. G., Kime K. K., Schrumpf M. E., Coe J. E., Simpson W. J. Antibody response in white-footed mice (Peromyscus leucopus) experimentally infected with the Lyme disease spirochete (Borrelia burgdorferi). Infect Immun. 1989 Nov;57(11):3445–3451. doi: 10.1128/iai.57.11.3445-3451.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Simpson W. J., Schrumpf M. E., Hayes S. F., Schwan T. G. Molecular and immunological analysis of a polymorphic periplasmic protein of Borrelia burgdorferi. J Clin Microbiol. 1991 Sep;29(9):1940–1948. doi: 10.1128/jcm.29.9.1940-1948.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Steere A. C. Lyme disease. N Engl J Med. 1989 Aug 31;321(9):586–596. doi: 10.1056/NEJM198908313210906. [DOI] [PubMed] [Google Scholar]
  40. Sădziene A., Rosa P. A., Thompson P. A., Hogan D. M., Barbour A. G. Antibody-resistant mutants of Borrelia burgdorferi: in vitro selection and characterization. J Exp Med. 1992 Sep 1;176(3):799–809. doi: 10.1084/jem.176.3.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wilske B., Anderson J. F., Baranton G., Barbour A. G., Hovind-Hougen K., Johnson R. C., Preac-Mursic V. Taxonomy of Borrelia spp. Scand J Infect Dis Suppl. 1991;77:108–129. [PubMed] [Google Scholar]
  42. Wilske B., Luft B., Schubach W. H., Zumstein G., Jauris S., Preac-Mursic V., Kramer M. D. Molecular analysis of the outer surface protein A (OspA) of Borrelia burgdorferi for conserved and variable antibody binding domains. Med Microbiol Immunol. 1992;181(4):191–207. doi: 10.1007/BF00215765. [DOI] [PubMed] [Google Scholar]
  43. Wilske B., Preac-Mursic V., Göbel U. B., Graf B., Jauris S., Soutschek E., Schwab E., Zumstein G. An OspA serotyping system for Borrelia burgdorferi based on reactivity with monoclonal antibodies and OspA sequence analysis. J Clin Microbiol. 1993 Feb;31(2):340–350. doi: 10.1128/jcm.31.2.340-350.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wilske B., Preac-Mursic V., Schierz G., Busch K. V. Immunochemical and immunological analysis of European Borrelia burgdorferi strains. Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):92–102. doi: 10.1016/s0176-6724(86)80108-0. [DOI] [PubMed] [Google Scholar]
  45. Wilske B., Preac-Mursic V., Schierz G., Gueye W., Herzer P., Weber K. Immunochemische Analyse der Immunantwort bei Spätmanifestationen der Lyme Borreliose. Zentralbl Bakteriol Mikrobiol Hyg A. 1988 Mar;267(4):549–558. [PubMed] [Google Scholar]
  46. Wilske B., Preac-Mursic V., Schierz G., Kühbeck R., Barbour A. G., Kramer M. Antigenic variability of Borrelia burgdorferi. Ann N Y Acad Sci. 1988;539:126–143. doi: 10.1111/j.1749-6632.1988.tb31846.x. [DOI] [PubMed] [Google Scholar]
  47. Zumstein G., Fuchs R., Hofmann A., Preac-Mursic V., Soutschek E., Wilske B. Genetic polymorphism of the gene encoding the outer surface protein A (OspA) of Borrelia burgdorferi. Med Microbiol Immunol. 1992;181(2):57–70. doi: 10.1007/BF00189424. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES