1887

Abstract

The aetiological agent of Lyme disease, cycles between its tick vector and mammalian hosts, implying that it can sense different environments and consequently change the expression of genes encoding several surface-associated proteins. The genome of the type strain B31 has revealed 175 different gene families. The gene, situated on the chromosome, encodes a channel-forming protein that belongs to the gene family 48 consisting of eight additional paralogous genes. The heterogeneity of the P13 protein from different Lyme disease strains was investigated. The predicted surface-exposed domains are the most heterogeneous regions and contain probable epitopes of P13. The membrane-spanning architecture of P13 was determined and a model for the location of this protein in the outer membrane is presented. The transcription of the paralogues of gene family 48 during culturing and in a mouse infection model was also analysed. The gene is the only paralogue present in all three Lyme-disease-causing genospecies; it is stable during cultivation and the BBA01 protein was expressed in all strains investigated. Conversely, paralogues , and were only detected in and the corresponding plasmids harbouring and were lost during passage. Finally, and are the only members of gene family 48 that are transcribed in mice, suggesting their importance during mammalian infection.

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2004-03-01
2024-04-23
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References

  1. 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]
  2. Appel R. D., Bairoch A., Hochstrasser D. F. 1994; A new generation of information retrieval tools for biologists: the example of the ExPASy WWW server. Trends Biochem Sci 19:258–260 [CrossRef]
    [Google Scholar]
  3. Aron L., Alekshun M., Perlee L., Schwartz I., Godfrey H. P., Cabello F. C. 1994; Cloning and DNA sequence analysis of bmpC, a gene encoding a potential membrane lipoprotein of Borrelia burgdorferi. FEMS Microbiol Lett 123:75–82 [CrossRef]
    [Google Scholar]
  4. Åsbrink E., Hederstedt B., Hovmark A. 1984; The spirochetal etiology of erythema chronicum migrans Afzelius. Acta Derm Venereol 64:291–295
    [Google Scholar]
  5. Baranton G., Marti Ras N., Postic D. 1998; Molecular epidemiology of the aetiological agents of Lyme borreliosis. Wien Klin Wochenschr 110:850–855
    [Google Scholar]
  6. Barbour A. G. 1984; Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med 57:521–525
    [Google Scholar]
  7. Barbour A. G. 1988; Plasmid analysis of Borrelia burgdorferi, the Lyme disease agent. J Clin Microbiol 26:475–478
    [Google Scholar]
  8. Barbour A. G. 1989; The molecular biology of Borrelia. Rev Infect Dis 11: Suppl 6S1470–S1474 [CrossRef]
    [Google Scholar]
  9. 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 [CrossRef]
    [Google Scholar]
  10. Bergström S., Olsen B., Burman N., Gothefors L., Jaenson T. G., Jonsson M., Mejlon H. A. 1992; Molecular characterization of Borrelia burgdorferi isolated from Ixodes ricinus in northern Sweden. Scand J Infect Dis 24:181–188 [CrossRef]
    [Google Scholar]
  11. Bono J. L., Elias A. F., Kupko J. J., 3rd, Stevenson B., Tilly K., Rosa P. 2000; Efficient targeted mutagenesis in Borrelia burgdorferi. J Bacteriol 182:2445–2452 [CrossRef]
    [Google Scholar]
  12. Bunikis J., Noppa L., Bergström S. 1995; Molecular analysis of a 66-kDa protein associated with the outer membrane of Lyme disease Borrelia. FEMS Microbiol Lett 131:139–145 [CrossRef]
    [Google Scholar]
  13. Bunikis J., Olsen B., Fingerle V., Bonnedahl J., Wilske B., Bergström S. 1996; Molecular polymorphism of the Lyme disease agent Borrelia garinii in northern Europe is influenced by a novel enzooticBorrelia focus in the North Atlantic. J Clin Microbiol 34:364–368
    [Google Scholar]
  14. Busch U., Will G., Hizo-Teufel C., Wilske B., Preac-Mursic V. 1997; Long-term in vitro cultivation of Borrelia burgdorferi sensu lato strains: influence on plasmid patterns, genome stability and expression of proteins. Res Microbiol 148:109–118 [CrossRef]
    [Google Scholar]
  15. Carlyon J. F., Roberts D. M., Marconi R. T. 2000; Evolutionary and molecular analyses of the Borrelia bdr super gene family: delineation of distinct sub-families and demonstration of the genus wide conservation of putative functional domains, structural properties and repeat motifs. Microb Pathog 28:89–105 [CrossRef]
    [Google Scholar]
  16. Carroll J. A., El-Hage N., Miller J. C., Babb K., Stevenson B. 2001; Borrelia burgdorferi RevA antigen is a surface-exposed outer membrane protein whose expression is regulated in response to environmental temperature and pH. Infect Immun 69:5286–5293 [CrossRef]
    [Google Scholar]
  17. Casjens S. 12 other authors Palmer N., van Vugt R. 2000; A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi. Mol Microbiol 35:490–516
    [Google Scholar]
  18. Feng S., Das S., Barthold S. W., Fikrig E. 1996; Characterization of two genes, p11 and p5, on the Borrelia burgdorferi 49-kilobase linear plasmid. Biochim Biophys Acta 1307:270–272 [CrossRef]
    [Google Scholar]
  19. 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 [CrossRef]
    [Google Scholar]
  20. Fukunaga M., Hamase A., Okada K., Nakao M. 1996; Borrelia tanukii sp. nov. and Borrelia turdae sp. nov. found from ixodid ticks in Japan: rapid species identification by 16S rRNA gene-targeted PCR analysis. Microbiol Immunol 40:877–881 [CrossRef]
    [Google Scholar]
  21. Gorbacheva V. Y., Godfrey H. P., Cabello F. C. 2000; Analysis of the bmp gene family in Borrelia burgdorferi sensu lato. J Bacteriol 182:2037–2042 [CrossRef]
    [Google Scholar]
  22. Grimm D., Elias A. F., Tilly K., Rosa P. A. 2003; Plasmid stability during in vitro propagation of Borrelia burgdorferi assessed at a clonal level. Infect Immun 71:3138–3145 [CrossRef]
    [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 [CrossRef]
    [Google Scholar]
  24. Hefty P. S., Brooks C. S., Jett A. M., White G. L., Wikel S. K., Kennedy R. C., Akins D. R. 2002; OspE-related, OspF-related, and Elp lipoproteins are immunogenic in baboons experimentally infected with Borrelia burgdorferi and in human Lyme disease patients. J Clin Microbiol 40:4256–4265 [CrossRef]
    [Google Scholar]
  25. Kawabata H., Masuzawa T., Yanagihara Y. 1993; Genomic analysis of Borrelia japonica sp. nov. isolated from Ixodes ovatus in Japan. Microbiol Immunol 37:843–848 [CrossRef]
    [Google Scholar]
  26. Kriuchechnikov V. N., Korenberg E. I., Shcherbakov S. V., Kovalevskii Iu V., Levin M. L. 1988; Identification of Borrelia isolated in the USSR from Ixodes persulcatus Schulze ticks. Zh Mikrobiol Epidemiol Immunobiol 12:41–44
    [Google Scholar]
  27. 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 [CrossRef]
    [Google Scholar]
  28. 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 [CrossRef]
    [Google Scholar]
  29. Le Fleche A., Postic D., Girardet K., Peter O., Baranton G. 1997; Characterization of Borrelia lusitaniae sp. nov. by 16S ribosomal DNA sequence analysis. Int J Syst Bacteriol 47:921–925 [CrossRef]
    [Google Scholar]
  30. Magnarelli L. A., Anderson J. F., Barbour A. G. 1989; Enzyme-linked immunosorbent assays for Lyme disease: reactivity of subunits of Borrelia burgdorferi. J Infect Dis 159:43–49 [CrossRef]
    [Google Scholar]
  31. McDowell J. V., Sung S. Y., Labandeira-Rey M., Skare J. T., Marconi R. T. 2001; Analysis of mechanisms associated with loss of infectivity of clonal populations of Borrelia burgdorferi B31MI. Infect Immun 69:3670–3677 [CrossRef]
    [Google Scholar]
  32. Miller J. C., Stevenson B. 2003; Immunological and genetic characterization of Borrelia burgdorferi BapA and EppA proteins. Microbiology 149:1113–1125 [CrossRef]
    [Google Scholar]
  33. Nilsson C. L., Cooper H. J., Håkansson K., Marshall A. G., Östberg Y., Lavrinovicha M., Bergström S. 2002; Characterization of the P13 membrane protein of Borrelia burgdorferi by mass spectrometry. J Am Soc Mass Spectrom 13:295–299 [CrossRef]
    [Google Scholar]
  34. Noppa L., Burman N., Sadziene A., Barbour A. G., Bergström S. 1995; Expression of the flagellin gene in Borrelia is controlled by an alternative sigma factor. Microbiology 141:85–93 [CrossRef]
    [Google Scholar]
  35. Noppa L., Östberg Y., Lavrinovicha M., Bergström S. 2001; P13, an integral membrane protein of Borrelia burgdorferi, is C-terminally processed and contains surface-exposed domains. Infect Immun 69:3323–3334 [CrossRef]
    [Google Scholar]
  36. Norris S. J., Howell J. K., Garza S. A., Ferdows M. S., Barbour A. G. 1995; High- and low-infectivity phenotypes of clonal populations of in vitro-cultured Borrelia burgdorferi. Infect Immun 63:2206–2212
    [Google Scholar]
  37. Ojaimi C., Brooks C., Casjens S.12 other authors 2003; Profiling of temperature-induced changes in Borrelia burgdorferi gene expression by using whole genome arrays. Infect Immun 71:1689–1705 [CrossRef]
    [Google Scholar]
  38. Ornstein K., Berglund J., Nilsson I., Norrby R., Bergström S. 2001; Characterization of Lyme borreliosis isolates from patients with erythema migrans and neuroborreliosis in southern Sweden. J Clin Microbiol 39:1294–1298 [CrossRef]
    [Google Scholar]
  39. Östberg Y., Pinne M., Benz R., Rosa P., Bergström S. 2002; Elimination of channel forming activity by insertional inactivation of the p13 gene inBorrelia burgdorferi. J Bacteriol 184:6811–6819 [CrossRef]
    [Google Scholar]
  40. Peter O., Bretz A. G. 1992; Polymorphism of outer surface proteins of Borrelia burgdorferi as a tool for classification. Zentbl Bakteriol 277:28–33 [CrossRef]
    [Google Scholar]
  41. Pinto do O. P., Kolterud Å., Carlsson L. 1998; Expression of the LIM-homeobox gene LH2 generates immortalized steel factor-dependent multipotent hematopoietic precursors. EMBO J 17:5744–5756 [CrossRef]
    [Google Scholar]
  42. Porcella S. F., Fitzpatrick C. A., Bono J. L. 2000; Expression and immunological analysis of the plasmid-borne mlp genes of Borrelia burgdorferi strain B31. Infect Immun 68:4992–5001 [CrossRef]
    [Google Scholar]
  43. Postic D., Ras N. M., Lane R. S., Hendson M., Baranton G. 1998; Expanded diversity among Californian borrelia isolates and description of Borrelia bissettii sp. nov. (formerly Borrelia group DN127). J Clin Microbiol 36:3497–3504
    [Google Scholar]
  44. 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 [CrossRef]
    [Google Scholar]
  45. Purser J. E., Lawrenz M. B., Caimano M. J., Howell J. K., Radolf J. D., Norris S. J. 2003; A plasmid-encoded nicotinamidase (PncA) is essential for infectivity of Borrelia burgdorferi in a mammalian host. Mol Microbiol 48:753–764 [CrossRef]
    [Google Scholar]
  46. Ramamoorthy R., Povinelli L., Philipp M. T. 1996; Molecular characterization, genomic arrangement, and expression of bmpD, a new member of the bmp class of genes encoding membrane proteins of Borrelia burgdorferi. Infect Immun 64:1259–1264
    [Google Scholar]
  47. Sadziene A., Thomas D. D., Barbour A. G. 1995; Borrelia burgdorferi mutant lacking Osp: biological and immunological characterization. Infect Immun 63:1573–1580
    [Google Scholar]
  48. Schwan T. G., Burgdorfer W., Garon C. F. 1988a; 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]
  49. Schwan T. G., Burgdorfer W., Schrumpf M. E., Karstens R. H. 1988b; The urinary bladder, a consistent source of Borrelia burgdorferi in experimentally infected white-footed mice (Peromyscus leucopus). J Clin Microbiol 26:893–895
    [Google Scholar]
  50. Shoberg R. J., Jonsson M., Sadziene A., Bergström S., Thomas D. D. 1994; Identification of a highly cross-reactive outer surface protein B epitope among diverse geographic isolates of Borrelia spp. causing Lyme disease. J Clin Microbiol 32:489–500
    [Google Scholar]
  51. Simpson W. J., Cieplak W., Schrumpf M. E., Barbour A. G., Schwan T. G. 1994; Nucleotide sequence and analysis of the gene in Borrelia burgdorferi encoding the immunogenic P39 antigen. FEMS Microbiol Lett 119:381–387 [CrossRef]
    [Google Scholar]
  52. Skare J. T., Champion C. I., Mirzabekov T. A.7 other authors 1996; Porin activity of the native and recombinant outer membrane protein Oms28 of Borrelia burgdorferi. J Bacteriol 178:4909–4918
    [Google Scholar]
  53. Steere A. C. 1989; Lyme disease. N Engl J Med 321:586–596 [CrossRef]
    [Google Scholar]
  54. 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]
  55. 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]
  56. 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 [CrossRef]
    [Google Scholar]
  57. 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 [CrossRef]
    [Google Scholar]
  58. Thomas V., Anguita J., Samanta S., Rosa P. A., Stewart P., Barthold S. W., Fikrig E. 2001; Dissociation of infectivity and pathogenicity in Borrelia burgdorferi. Infect Immun 69:3507–3509 [CrossRef]
    [Google Scholar]
  59. Wang G., van Dam A. P., Le Fleche A., Postic D., Peter O., Spanjaard L., Dankert J., Baranton G., de Boer R. 1997; Genetic and phenotypic analysis of Borrelia valaisianasp. nov. (Borrelia genomic groups VS116 and M19). Int J Syst Bacteriol 47:926–932 [CrossRef]
    [Google Scholar]
  60. Wang G., van Dam A. P., Dankert J. 2001; Analysis of a VMP-like sequence (vls) locus in Borrelia garinii and Vls homologues among four Borrelia burgdorferi sensu lato species. FEMS Microbiol Lett 199:39–45 [CrossRef]
    [Google Scholar]
  61. 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]
  62. 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]
  63. Yang X., Popova T. G., Hagman K. E., Wikel S. K., Schoeler G. B., Caimano M. J., Radolf J. D., Norgard M. V. 1999; Identification, characterization, and expression of three new members of the Borrelia burgdorferi Mlp (2·9) lipoprotein gene family. Infect Immun 67:6008–6018
    [Google Scholar]
  64. Yang X., Goldberg M. S., Popova T. G., Schoeler G. B., Wikel S. K., Hagman K. E., Norgard M. V. 2000; Interdependence of environmental factors influencing reciprocal patterns of gene expression in virulent Borrelia burgdorferi. Mol Microbiol 37:1470–1479 [CrossRef]
    [Google Scholar]
  65. Zhang J. R., Norris S. J. 1998a; Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion. Infect Immun 66:3698–3704
    [Google Scholar]
  66. Zhang J. R., Norris S. J. 1998b; Kinetics and in vivo induction of genetic variation of vlsE in Borrelia burgdorferi. Infect Immun 66:3689–3697
    [Google Scholar]
  67. Zhang J. R., Hardham J. M., Barbour A. G., Norris S. J. 1997; Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes. Cell 89:275–285 [CrossRef]
    [Google Scholar]
  68. Zuckert W. R., Meyer J., Barbour A. G. 1999; Comparative analysis and immunological characterization of the Borrelia Bdr protein family. Infect Immun 67:3257–3266
    [Google Scholar]
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