1887

Abstract

A large majority of examined Lyme disease spirochaete isolates were demonstrated to contain one or both of the paralogous genes and . Immunological analyses of serum samples collected from infected patients coupled with comparative sequence analyses indicated that gene sequences are quite stable but the encoded proteins do not provoke a strong immune response in most individuals. Conversely, EppA proteins are much more antigenic but vary widely in sequence between different bacteria. Considerable evidence of insertion, deletion and other mutations within genes was observed. A number of significant recombination events were also found to have occurred in regions flanking genes, while the genes themselves rarely exhibited evidence of mutation, suggesting strong selective pressure to maintain BapA sequences within narrow limits. Data from these and other studies suggest important roles for BapA and EppA during the infectious cycle.

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2003-05-01
2024-04-23
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References

  1. Akins D. R., Porcella S. F., Popova T. G., Shevchenko D., Baker S. I., Li M., Norgard M. V., Radolf J. D. 1995; Evidence for in vivo but not in vitro expression of a Borrelia burgdorferi outer surface protein F (OspF) homologue. Mol Microbiol 18:507–520
    [Google Scholar]
  2. Akins D. R., Caimano M. J., Yang X., Cerna F., Norgard M. V., Radolf J. D. 1999; Molecular and evolutionary analysis of Borrelia burgdorferi 297 circular plasmid-encoded lipoproteins with OspE- and OspF-like leader peptides. Infect Immun 67:1526–1532
    [Google Scholar]
  3. Alitalo A., Meri T., Lankinen H., Seppälä I., Lahdenne P., Hefty P. S., Akins D., Meri S. 2002; Complement inhibitor factor H binding to Lyme disease spirochetes is mediated by inducible expression of multiple plasmid-encoded outer surface protein E paralogs. J Immunol 169:3847–3853
    [Google Scholar]
  4. Amouriaux P., Assous M., Margarita D., Baranton G., Saint Girons I. 1993; Polymerase chain reaction with the 30-kb circular plasmid of Borrelia burgdorferi B31 as a target for detection of the Lyme borreliosis agents in cerebrospinal fluid. Res Microbiol 144:211–219
    [Google Scholar]
  5. Baranton G., Postic D., Saint Girons I., Boerlin P., Piffaretti J.-C., Assous M., Grimont P. A. D. 1992; Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461 associated with Lyme borreliosis. Int J Syst Bacteriol 42:378–383
    [Google Scholar]
  6. Barbour A. G. 1984; Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med 57:521–525
    [Google Scholar]
  7. Barthold S. W., Moody K. D., Terwilliger G. A., Duray P. H., Jacoby R. O., Steere A. C. 1988; Experimental Lyme arthritis in rats infected with Borrelia burgdorferi . J Infect Dis 157:842–846
    [Google Scholar]
  8. Bauer Y., Hofmann H., Jahraus O., Mytilineos J., Simon M. M., Wallich R. 2001; Prominent T cell response to a selectively in vivo expressed Borrelia burgdorferi outer surface protein (pG) in patients with Lyme disease. Eur J Immunol 31:767–776
    [Google Scholar]
  9. Belland R. J., Morrison S. G., van der Ley P., Swanson J. 1989; Expression and phase variation of gonnococcal P.II genes in Escherichia coli involves ribosomal frameshifting and slipped-strand mispairing. Mol Microbiol 3:777–786
    [Google Scholar]
  10. Bissett M. L., Hill W. 1987; Characterization of Borrelia burgdorferi strains isolated from Ixodes pacificus ticks in California. J Clin Microbiol 25:2296–2301
    [Google Scholar]
  11. Burgdorfer W., Barbour A. G., Hayes S. F., Benach J. L., Grunwaldt E., Davis J. P. 1982; Lyme disease – a tick-borne spirochetosis?. Science 216:1317–1319
    [Google Scholar]
  12. Casjens S., van Vugt R., Tilly K., Rosa P. A., Stevenson B. 1997; Homology throughout the multiple 32-kilobase circular plasmids present in Lyme disease spirochetes. J Bacteriol 179:217–227
    [Google Scholar]
  13. Casjens S., Palmer N., van Vugt R. 12 other authors 2000; A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs of an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi . Mol Microbiol 35:490–516
    [Google Scholar]
  14. Champion C. I., Blanco D. R., Skare J. T., Haake D. A., Giladi M., Foley D., Miller J. N., Lovett M. A. 1994; A 9·0-kilobase-pair circular plasmid of Borrelia burgdorferi encodes an exported protein: evidence for expression only during infection. Infect Immun 62:2653–2661
    [Google Scholar]
  15. Cinco M., Banfi E., Balanzin D., Caccio S., Graziosi G., Fattorini P. 1989; Restriction endonuclease analysis of four Borrelia burgdorferi strains. FEMS Microbiol Immunol 1:511–514
    [Google Scholar]
  16. Dunn J. J., Buchstein S. R., Butler L.-L., Fisenne S., Polin D. S., Lade B. N., Luft B. J. 1994; Complete nucleotide sequence of a circular plasmid from the Lyme disease spirochete, Borrelia burgdorferi . J Bacteriol 176:2706–2717
    [Google Scholar]
  17. Dykhuizen D. E., Baranton G. 2001; Implications of a low rate of horizontal transfer in Borrelia . Trends Microbiol 9:344–350
    [Google Scholar]
  18. Eberhard W. G. 1989; Why do bacterial plasmids carry some genes and not others?. Plasmid 21:167–174
    [Google Scholar]
  19. Eggers C. H., Caimano M. J., Clawson M. L., Miller W. G., Samuels D. S., Radolf J. D. 2002; Identification of loci critical for replication and compatibility of a Borrelia burgdorferi cp32 plasmid and use of a cp32-based shuttle vector for the expression of fluorescent reporters in the Lyme disease spirochaete. Mol Microbiol 43:281–295
    [Google Scholar]
  20. El-Hage N., Lieto L. D., Stevenson B. 1999; Stability of erp loci during Borrelia burgdorferi infection: recombination is not required for chronic infection of immunocompetent mice. Infect Immun 67:3146–3150
    [Google Scholar]
  21. El-Hage N., Babb K., Carroll J. A., Lindstrom N., Fischer E. R., Miller J. C., Gilmore R. D. Jr, Mbow M. L., Stevenson B. 2001; Surface exposure and protease insensitivity of Borrelia burgdorferi Erp (OspEF-related) lipoproteins. Microbiology 147:821–830
    [Google Scholar]
  22. Fraser C. M., Casjens S., Huang W. M. 35 other authors 1997; Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi . Nature 390:580–586
    [Google Scholar]
  23. Hefty P. S., Jolliff S. E., Caimano M. J., Wikel S. K., Radolf J. D., Akins D. R. 2001; Regulation of OspE-related, OspF-related, and Elp lipoproteins of Borrelia burgdorferi strain 297 by mammalian host-specific signals. Infect Immun 69:3618–3627
    [Google Scholar]
  24. Hellwage J., Meri T., Heikkilä T., Alitalo A., Panelius J., Lahdenne P., Seppälä I. J. T., Meri S. 2001; The complement regulatory factor H binds to the surface protein OspE of Borrelia burgdorferi . J Biol Chem 276:8427–8435
    [Google Scholar]
  25. Hughes C. A. N., Kodner C. B., Johnson R. C. 1992; DNA analysis of Borrelia burgdorferi NCH-1, the first northcentral U.S. human Lyme disease isolate. J Clin Microbiol 30:698–703
    [Google Scholar]
  26. Hyde F. W., Johnson R. C. 1988; Characterization of a circular plasmid from Borrelia burgdorferi , etiologic agent of Lyme disease. J Clin Microbiol 26:2203–2205
    [Google Scholar]
  27. Hynes R. O. 1992; Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25
    [Google Scholar]
  28. Jeanmougin F., Thompson J. D., Gouy M., Higgins D. G., Gibson T. J. 1998; Multiple sequence alignment with Clustal X. Trends Biochem Sci 23:403–405
    [Google Scholar]
  29. Kraiczy P., Skerka C., Brade V., Zipfel P. F. 2001a; Further characterization of complement regulator-acquiring surface proteins of Borrelia burgdorferi . Infect Immun 69:7800–7809
    [Google Scholar]
  30. Kraiczy P., Skerka C., Kirschfink M., Brade V., Zipfel P. F. 2001b; Immune evasion of Borrelia burgdorferi by acquisition of human complement regulators FHL-1/reconectin and factor H. Eur J Immunol 31:1674–1684
    [Google Scholar]
  31. Kryuchechnikov V. N., Korenberg E. I., Shcherbakov S. V., Kovalevsky Y. V., Levin M. L. 1988; Identification of Borrelia isolated in the USSR from Ixodes persulcatus Schulze ticks. J Microbiol Epidemiol Immunobiol 12:41–44
    [Google Scholar]
  32. Kurtenbach K., DeMichelis S., Etti S., Schäfer S. M., Sewell H.-S., Brade V., Kraiczy P. 2002a; Host association of Borrelia burgdorferi sensu lato - the key role of host complement. Trends Microbiol 10:74–79
    [Google Scholar]
  33. Kurtenbach K., Schäfer S. M., Sewell H.-S., Peacey M., Hoodless A., Nuttall P. A., Randolph S. E. 2002b; Differential survival of Lyme borreliosis spirochetes in ticks that feed on birds. Infect Immun 70:5893–5895
    [Google Scholar]
  34. Kurtti T. J., Munderloh U. G., Johnson R. C., Ahlstrand G. G. 1987; Colony formation and morphology in Borrelia burgdorferi . J Clin Microbiol 25:2054–2058
    [Google Scholar]
  35. Labandeira-Rey M., Skare J. T. 2001; Decreased infectivity in Borrelia burgdorferi strain B31 is associated with loss of linear plasmid 25 or 28-1. Infect Immun 69:446–455
    [Google Scholar]
  36. Labandeira-Rey M., Baker E. A., Skare J. T. 2001; VraA (BBI16) protein of Borrelia burgdorferi is a surface-exposed antigen with a repetitive motif that confers partial protection against experimental Lyme borreliosis. Infect Immun 69:1409–1419
    [Google Scholar]
  37. Lam T. T., Nguyen T.-P. K., Montgomery R. R., Kantor F. S., Fikrig E., Flavell R. A. 1994; Outer surface proteins E and F of Borrelia burgdorferi , the agent of Lyme disease. Infect Immun 62:290–298
    [Google Scholar]
  38. Liang F. T., Nelson F. K., Fikrig E. 2002; DNA microarray assessment of putative Borrelia burgdorferi lipoprotein genes. Infect Immun 70:3300–3303
    [Google Scholar]
  39. Marconi R. T., Konkel M. E., Garon C. F. 1993; Variability of osp genes and gene products among species of Lyme disease spirochetes. Infect Immun 61:2611–2617
    [Google Scholar]
  40. Masuzawa T., Okada Y., Beppu Y., Oku T., Kawamori F., Yanagihara Y. 1991; Immunological properties of Borrelia burgdorferi isolated from the Ixodes ovatus in Shizuoka, Japan. Microbiol Immunol 35:913–919
    [Google Scholar]
  41. McLean R. G., Ubico S. R., Hughes C. A., Engstrom S. M., Johnson R. C. 1993; Isolation and characterization of Borrelia burgdorferi from blood of a bird captured in the Saint Croix River Valley. J Clin Microbiol 31:2038–2043
    [Google Scholar]
  42. Miller J. C., Bono J. L., Babb K., El-Hage N., Casjens S., Stevenson B. 2000a; A second allele of eppA in Borrelia burgdorferi strain B31 is located on the previously undetected circular plasmid cp9-2. J Bacteriol 182:6254–6258
    [Google Scholar]
  43. Miller J. C., El-Hage N., Babb K., Stevenson B. 2000b; Borrelia burgdorferi B31 Erp proteins that are dominant immunoblot antigens of animals infected with isolate B31 are recognized by only a subset of human Lyme disease patient sera. J Clin Microbiol 38:1569–1574
    [Google Scholar]
  44. Murphy G. L., Connell T. D., Barritt D. S., Koomey M., Cannon J. G. 1989; Phase variation of gonnococcal protein II: regulation of gene expression by slipped strand mispairing of a repetitive DNA sequence. Cell 56:539–547
    [Google Scholar]
  45. Nohlmans L., de Boer R., van den Bogaard A., van Boven C. 1995; Genotypic and phenotypic analysis of Borrelia burgdorferi isolates from the Netherlands. J Clin Microbiol 33:119–125
    [Google Scholar]
  46. Postic D., Assous M. V., Grimont P. A. D., Baranton G. 1994; Diversity of Borrelia burgdorferi sensu lato evidenced by restriction fragment length polymorphism of rrf (5S)- rrl (23S) intergenic spacer amplicons. Int J Syst Bacteriol 44:743–752
    [Google Scholar]
  47. Purser J. E., Norris S. J. 2000; Correlation between plasmid content and infectivity in Borrelia burgdorferi . Proc Natl Acad Sci U S A 97:13865–13870
    [Google Scholar]
  48. Qiu W.-G., Dykhuizen D. E., Acosta M. S., Luft B. J. 2002; Geographic uniformity of the Lyme disease spirochete ( Borrelia burgdorferi ) and its shared history with tick vector ( Ixodes scapularis ) in the northeastern United States. Genetics 160:833–849
    [Google Scholar]
  49. Roberts W. C., Mullikin B. A., Lathigra R., Hanson M. S. 1998; Molecular analysis of sequence heterogeneity among genes encoding decorin binding proteins A and B of Borrelia burgdorferi sensu lato. Infect Immun 66:5275–5285
    [Google Scholar]
  50. Rosa P., Samuels D. S., Hogan D., Stevenson B., Casjens S., Tilly K. 1996; Directed insertion of a selectable marker into a circular plasmid of Borrelia burgdorferi . J Bacteriol 178:5946–5953
    [Google Scholar]
  51. Schwan T. G., Burgdorfer W., Garon C. F. 1988; Changes in infectivity and plasmid profile of the Lyme disease spirochete, Borrelia burgdorferi , as a result of in vitro cultivation. Infect Immun 56:1831–1836
    [Google Scholar]
  52. Schwan T. G., Schrumpf M. E., Karstens R. H., Clover J. R., Wong J., Daugherty M., Struthers M., Rosa P. A. 1993; Distribution and molecular analysis of Lyme disease spirochetes, Borrelia burgdorferi , isolated from ticks throughout California. J Clin Microbiol 31:3096–3108
    [Google Scholar]
  53. Shapiro J. A. 1983 Mobile Genetic Elements New York: Academic Press;
    [Google Scholar]
  54. Simpson W. J., Schrumpf M. E., Schwan T. G. 1990; Reactivity of human Lyme borreliosis sera with a 39-kilodalton antigen specific to Borrelia burgdorferi . J Clin Microbiol 28:1329–1337
    [Google Scholar]
  55. Steere A. C., Grodzicki R. L., Craft J. E., Shrestha M., Kornblatt A. N., Malawista S. E. 1984; Recovery of Lyme disease spirochetes from patients. Yale J Biol Med 57:557–560
    [Google Scholar]
  56. Stevenson B., Barthold S. W. 1994; Expression and sequence of outer surface protein C among North American isolates of Borrelia burgdorferi . FEMS Microbiol Lett 124:367–372
    [Google Scholar]
  57. Stevenson B., Tilly K., Rosa P. A. 1996; A family of genes located on four separate 32-kilobase circular plasmids in Borrelia burgdorferi B31. J Bacteriol 178:3508–3516
    [Google Scholar]
  58. Stevenson B., Casjens S., van Vugt R., Porcella S. F., Tilly K., Bono J. L., Rosa P. 1997; Characterization of cp18, a naturally truncated member of the cp32 family of Borrelia burgdorferi plasmids. J Bacteriol 179:4285–4291
    [Google Scholar]
  59. Stevenson B., Bono J. L., Schwan T. G., Rosa P. 1998a; Borrelia burgdorferi Erp proteins are immunogenic in mammals infected by tick bite, and their synthesis is inducible in cultured bacteria. Infect Immun 66:2648–2654
    [Google Scholar]
  60. Stevenson B., Casjens S., Rosa P. 1998b; Evidence of past recombination events among the genes encoding the Erp antigens of Borrelia burgdorferi . Microbiology 144:1869–1879
    [Google Scholar]
  61. Stevenson B., Zückert W. R., Akins D. R. 2001; Repetition, conservation, and variation: the multiple cp32 plasmids of Borrelia species. In The Spirochetes: Molecular and Cellular Biology pp  87–100 Edited by Saier M. H., García-Lara J. Oxford: Horizon Press;
    [Google Scholar]
  62. Stevenson B., El-Hage N., Hines M. A., Miller J. C., Babb K. 2002; Differential binding of host complement inhibitor factor H by Borrelia burgdorferi Erp surface proteins: a possible mechanism underlying the expansive host range of Lyme disease spirochetes. Infect Immun 70:491–497
    [Google Scholar]
  63. Stewart P. E., Thalken R., Bono J. L., Rosa P. 2001; Isolation of a circular plasmid region sufficient for autonomous replication and transformation of infectious Borrelia burgdorferi . Mol Microbiol 39:714–721
    [Google Scholar]
  64. Swofford D. L. 2000 PAUP*, Phylogenetic Analysis Using Parsimony (*and Other Methods) , version 4 Sunderland, MA: Sinauer Associates;
    [Google Scholar]
  65. Wallich R., Brenner C., Kramer M. D., Simon M. M. 1995; Molecular cloning and immunological characterization of a novel linear-plasmid-encoded gene, pG , of Borrelia burgdorferi expressed only in vivo. Infect Immun 63:3327–3335
    [Google Scholar]
  66. Wang G., Ojaimi C., Iyer R., Saksenberg V., McClain S. A., Wormser G. P., Schwartz I. A. 2001; Impact of genotypic variation of Borrelia burgdorferi sensu stricto on kinetics of dissemination and severity of disease in C3H/HeJ mice. Infect Immun 69:4303–4312
    [Google Scholar]
  67. Xu Y., Johnson R. C. 1995; Analysis and comparison of plasmid profiles of Borrelia burgdorferi sensu lato strains. J Clin Microbiol 33:2679–2685
    [Google Scholar]
  68. Xu Y., Kodner C., Coleman L., Johnson R. C. 1996; Correlation of plasmids with infectivity of Borrelia burgdorferi sensu stricto type strain B31. Infect Immun 64:3870–3876
    [Google Scholar]
  69. Yogev D., Rosengarten R., Watson-McKown R., Wise K. S. 1991; Molecular basis of Mycoplasma surface antigenic variation: a novel set of divergent genes undergo spontaneous mutation of periodic coding regions and 5′ regulatory sequences. EMBO J 10:4069–4079
    [Google Scholar]
  70. Zimmer G., Schaible U. E., Kramer M. D., Mall G., Museteanu C., Simon M. M. 1990; Lyme carditis in immunodeficient mice during experimental infection of Borrelia burgdorferi . Virchows Arch Pathol Ana Histopathol 417:129–135
    [Google Scholar]
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