Antigenic Variation in Borrelial Diseases of Humans

  • Alan G. Barbour


Relapsing fever and Lyme disease are human infections caused by different members of the spirochetal genus Borrelia (1). In both diseases a spirochetemia in the vertebrate is the source of infection for the arthropod. One presumes that a bacterium persisting in the blood of the vertebrate longer than another bacterium would have a selective advantage over its more short-lived siblings. It is not surprising, therefore, to find that one of the strategies used by borrelias to achieve this persistence in the host is antigenic variation.


Lyme Disease Antigenic Variation Borrelia Burgdorferi Major Outer Membrane Protein Lyme Arthritis 
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  1. 1.
    Barbour AG, Hayes SF (1986) Biology of Borrelia species. Microbiol Rev 50: 351–400Google Scholar
  2. 2.
    Woese CR (1987) Bacterial evolution. Microbiol Rev 51: 221–271PubMedGoogle Scholar
  3. 3.
    Holt SC (1978) Anatomy and chemistry of spirochetes. Microbiol Rev 42: 1 14–160Google Scholar
  4. 4.
    Saint Giron I, Barbour AG (1991) Antigenic variation in Borrelia. Res Microbiol 142: 114–160Google Scholar
  5. 5.
    Obermeier O (1573) Vorkommen feinster eine Eigenbewegung zeigender Faden im Blute von Rekurrenskranken. Zentralbl Med Wiss 11: 145–155Google Scholar
  6. 6.
    Swellengrebel NH (1907) Sur la cytologie compare des spirochetes et des spirilles. Ann Inst Pasteur 21: 562–586Google Scholar
  7. 7.
    Nicolle C, Blaizot L, Conseil E (1913) Etiologie de la fievre recurrente. Son mode de transmission par les poux. Ann Inst Pasteur 27: 204–225Google Scholar
  8. 8.
    Schmid GP (1985) The global distribution of Lyme disease. Rev Infect Dis 7: 41–50PubMedCrossRefGoogle Scholar
  9. 9.
    Steere AC, Malawista SE, Syndman DR (1977) Lyme arthritis: an epidemic of oligo-articular arthritis in children and adults in three Connecticut communities. Arthritis Rheum 20: 7–17PubMedCrossRefGoogle Scholar
  10. 10.
    Burgdorfer W, Barbour AG, Hayes SF, Benach JL, Grunwaldt E, Davis JP (1982) Lyme disease — a tick-borne spirochetosis? Science 216: 1317–1319PubMedCrossRefGoogle Scholar
  11. 11.
    Barbour AG (1988a) Laboratory aspects of Lyme disease. Clin Microbiol Rev 1: 399–414PubMedGoogle Scholar
  12. 12.
    Barbour AG (1987) Immunobiology of relapsing fever. Contrib Microbiol Immmunol 8: 125–137Google Scholar
  13. 13.
    Barbour AG (1990) Antigenic variation of a relapsing fever Borrelia species. Ann Rev Microbiol 44: 155–171CrossRefGoogle Scholar
  14. 14.
    Goldsmid JM, Mahomed K(1972) The use of the microhematocrit technique for the recovery of Borrelia duttonii from the blood. Am J Clin Pathol 58: 165–169PubMedGoogle Scholar
  15. 15.
    Coffey EM, Evelund WC (1967) Experimentaf relapsing fever initiated by Borrelia hermsii. II. Sequential appearance of major serotypes in the rat. T Infect Dis 117: 29–34CrossRefGoogle Scholar
  16. 16.
    Stoenner HG, Todd T, Larsen C (1982) Antigenic variation of Borrelia hermsii. J Exp Med 156: 1297–1311PubMedCrossRefGoogle Scholar
  17. 17.
    Barbour AG, Barrera O, Judd RC (1983) Structural analysis of the variable major proteins of Borrelia hermsii. J Exp Med 158: 2127–2140PubMedCrossRefGoogle Scholar
  18. 18.
    Barbour AG, Tessier SL, Stoenner HG (1982) Variable major proteins of Borrelia hermsii. J Exp Med 156: 1312–1324PubMedCrossRefGoogle Scholar
  19. 19.
    Barstad PA, Coligan JE, Raum MG, Barbour AG (1985) Variable major proteins of Borrelia hermsii: epitope mapping and partial sequence analysis of CNBr peptides. J Exp Med 161: 1302–1314PubMedCrossRefGoogle Scholar
  20. 20.
    Burman NS, Bergström S, Restrepo BI, Barbour AG (1990) The variable antigens Vmp7 and Vmp21 of the relapsing fever bacterium Borrelia hermsii are structurally analogous to the VSG proteins of the African trypanosome. Mol Microbiol 4: 1715–1726PubMedCrossRefGoogle Scholar
  21. 21.
    Meier JT, Simon MI, Barbour AG (1985) Antigenic variation is associated with DNA rearrangements in a relapsing fever Borrelia sp. Cell 41: 403–409PubMedCrossRefGoogle Scholar
  22. 22.
    Plasterk RHA, Simon MI, Barbour AG (1985) Transposition of structural genes to an expression sequence on a linear plasmid causes antigenic variation in Borrelia hermsii. Nature (London) 318: 257–263CrossRefGoogle Scholar
  23. 23.
    Kitten T, Barbour AG (1990) Juxtaposition of expressed variable antigen genes with a conserved telomere in the bacterium Borrelia hermsii. Proc Natl Acad Sci (USA) 87: 6077— 6081CrossRefGoogle Scholar
  24. 24.
    Barbour AG, Burman N, Carter CJ, Kitten T, Bergström S (1991a) Variable antigen genes of the relapsing fever agent Borrelia hermsii are activated by promoter addition. Mol Microbiol 5: 489–493PubMedCrossRefGoogle Scholar
  25. 25.
    Barbour AG (1989) Antigenic variation in a relapsing fever Borrelia: genetic aspects. In: Berg De, Howe MM (eds) Mobile DNA. Washington, American Society for Microbiology, 783–789Google Scholar
  26. 26.
    Barbour AG, Carter CJ, Burman N, Freitag CS, Garon CF, Bergström S (1991 b) Tandem insertion sequence-like elements define the expression site for variable antigen genes of Borrelia hermsii. Infect Immun 59: 390–397PubMedGoogle Scholar
  27. 27.
    Burgdorfer W, Gage KL (1986) Susceptibility of the black-legged tick, Ixodes scapularis, to the Lyme disease spirochete, Borrelia burgdorferi. Zentralbl Bakteriol Parasitenkd Infektionskr Hyg Abt 1 Orig Reihe A 263: 15–20Google Scholar
  28. 28.
    Burgdorfer W, Gage KL (1987) Susceptibility of the hispid cotton rat (Sigmodon hispidus) to the Lyme disease spirochete (Borrelia burgdorferi) . Am J Trop Med Hyg 37: 624–628PubMedGoogle Scholar
  29. 29.
    Stanek G, Burger I, Hirschl A, Wewalka G, Radda A (1986) Borrelia transfer by ticks during their life cycle. Studies of laboratory animals. Zentralbl Bakteriol Parasitenkd Infektionskr Hyg Abt 1 Orig Reihe A 263: 29–33Google Scholar
  30. 30.
    Craft JE, Fischer DK, Shimamoto GT, Steere AC (1986) Antigens of Borrelia burgdorferi recognized during Lyme disease. Appearance of a new IgM response and expansion of the IgG response late in illness. J Clin Invest 78: 934–939PubMedCrossRefGoogle Scholar
  31. 31.
    Howe TR, Mayer LW, Barbour AG (1985) A single recombinant plasmid expressing two major outer surface proteins of the Lyme disease spirochete. Science 227: 645–646PubMedCrossRefGoogle Scholar
  32. 32.
    Howe TR, LaQuier FW, Barbour AG (1986) Organization of genes encoding two outer membrane proteins of the Lyme disease agent Borrelia burgdorferi within a single transcriptional unit. Infect Immun 54: 207–212PubMedGoogle Scholar
  33. 33.
    Bergström S, Bundoc VG, Barbour AG (1989) Molecular analysis of linear plasmid-encoded major proteins, OspA and OspB, of the Lyme disease spirochete, Borrelia burgdorferi. Mol Microbiol 3: 479–486PubMedCrossRefGoogle Scholar
  34. 34.
    Brandt ME, Riley BS, Radolf JD, Norgard MV (1990) Immunogenic integral membrane proteins of Borrelia burgdorferi are lipoproteins. Infect Immun 58: 983–989PubMedGoogle Scholar
  35. 35.
    Barbour AG, Tessier SL, Hayes SF (1984) Variation in a major surface protein of Lyme disease spirochetes. Infect Immun 45: 94–100PubMedGoogle Scholar
  36. 36.
    Barbour AG, Heiland RA, Howe TR (1985) Heterogeneity of major proteins in Lyme disease borreliae: a molecular analysis of North American and European isolates. J Infect Dis 152: 478–484PubMedCrossRefGoogle Scholar
  37. 37.
    Barbour AG, Schrumpf ME (1986) Polymorphisms of major surface proteins of Borrelia burgdorferi. Zentralbl Bakteriol Hyg A 263: 83–91Google Scholar
  38. 38.
    Wilske B, Preac-Mursic V, Schierz G, Busch KV (1986) Immunochemical and immunological analysis of European Borrelia burgdorferi strains. Zentralbl Bakteriol Mikrobiol Hyg [A] 263: 92–102Google Scholar
  39. 39.
    Wilske B, Preac-Mursic V, Schier G, Kuhbeck R, Barbour AG, Kramer M (1988) Antigenic variability of Borrelia burgdorferi. Ann NY Acad Sci 539: 126–143PubMedCrossRefGoogle Scholar
  40. 40.
    Bissett ML, Hill W (1987) Characterization of Borrelia burgdorferi strains isolated from Ixodes pacificus ticks in California. J Clin Microbiol 25: 2296–2301PubMedGoogle Scholar
  41. 41.
    Kryuchechnikov VN, Korenberg EI, Scherbakov SV, Yovalesky YuV, Levin ML (1988) Identification of Borrelia isolated in the USSR from Ixodes persulcatus schulze ticks. J Microbiol Epidemiol Immunobiol 12: 41–44Google Scholar
  42. 42.
    Anderson JF, Magnarelli LA, McAninch JB (1988) Borrelia burgdorferi antigenic variant isolated from Ixodes dammini from upstate New York. J Clin Microbiol 26: 2209–2212PubMedGoogle Scholar
  43. 43.
    Anderson JF, Magnarelli LA, LeFebvre RB, Andreadis TG, McAninch JB, Perng G-C, Johnson RC (1989) Antigenically variable Borrelia burgdorferi isolated from cotton-tail rabbits and Ixodes dentatus in rural and urban areas. J Clin Microbiol 27: 13–20PubMedGoogle Scholar
  44. 44.
    Lane RS, Pascocello JA (1989) Antigenic characteristics of Borrelia burgdorferi isolates from ixodid ticks in California. J Clin Microbiol 27: 2344–2349PubMedGoogle Scholar
  45. 45.
    Schwan TG, Kime KK, Schrumpf ME, Coe JE, Simpson WJ (1989) Antibody response in white-footed mice (Peromyscus leukopus) experimentally infected with the Lyme disease spirochete (Borrelia burgdorferi) . Infect Immun 57: 3445–3451PubMedGoogle Scholar
  46. 46.
    Schwan TG, Burgdorfer W (1987) Antigenic changes of Borrelia burgdorferi as a result of in vitro cultivation. J Infect Dis 156: 852–853PubMedCrossRefGoogle Scholar
  47. 47.
    Schwan TG, Burgdorfer W, Garon CF (1988) Changes in infectivity and plasmid profile of the Lyme disease spirochete Borrelia burgdorferi as a result of in vitro cultivation. Infec_t Immun 56: 1831–1836Google Scholar
  48. 48.
    Bundoc VG, Barbour AG (1989) Clonal polymorphisms of outer membrane protein OspB of Borrelia burgdorferi. Infect Immun 57: 2733–2741PubMedGoogle Scholar
  49. 49.
    Luft BJ, Jiang W, Munoz P, Dattwyler RJ, Gorevic PD (1989) Biochemical and immunological characterization of the surface proteins of Borrelia burgdorferi. Infect Immun 57: 3637–3645PubMedGoogle Scholar
  50. 50.
    Barbour AG (1988b) Plasmid analysis of Borrelia burgdorferi, the Lyme disease agent. J Clin Microbiol 26: 475–478PubMedGoogle Scholar
  51. 51.
    Barbour AG, Tessier SL, Todd WJ (1983) Lyme disease spirochetes and Ixodidi tick spirochetes share a common surface antigenic determinant defined by a monoclonal antibody. Infect Immun 41: 795–804PubMedGoogle Scholar
  52. 52.
    Milch LJ, Barbour AG (1989) Analysis of North American and European isolates of Borrelia burgdorferi with antiserum to a recombinant antigen. J Infect 1is 160: 351–353CrossRefGoogle Scholar
  53. 53.
    Barbour AG, Garon CF (1987) Linear plasmids of the bacterium Borrelia burgdorferi have covalently-closed ends. Science 237: 409–411PubMedCrossRefGoogle Scholar
  54. 54.
    Barbour AG, Garon CF (1988) The genes encoding major surface proteins of Borrelia burgdorferi are located on a plasmid. Ann NYAcad Sci 539: 144–153PubMedCrossRefGoogle Scholar
  55. 55.
    Hindersson P, Hansen K, Fjordvang H, Pallesen L (1990) Abstract #D-136. American Society for Microbiology Annual MeetingGoogle Scholar
  56. 56.
    Sadziene A, Thomas DD, Bundoc VG, Holt SC, Barbour AG (1991) A flagella-less mutant of Borrelia burgdorferi: structural, molecular, and in vitro functional characterization. J Clin Invest 88: 82–92PubMedCrossRefGoogle Scholar
  57. 57.
    Hinnebusch J, Bergstrom S, Barbour AG (1990) Cloning and sequence analysis of linear plasmid telomeres of the bacterium Borrelia burgdorferi. Mol Microbiol 4: 811–820PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Alan G. Barbour
    • 1
  1. 1.Departments of Medicine and MicrobiologyThe University of Texas Health Science CenterSan AntonioUSA

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