Skip to main content
PMC home page
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1993 May;175(9):2516–2522. doi: 10.1128/jb.175.9.2516-2522.1993

Intragenic recombination and a chimeric outer membrane protein in the relapsing fever agent Borrelia hermsii.

T Kitten 1, A V Barrera 1, A G Barbour 1
PMCID: PMC204552  PMID: 7683020

Abstract

The spirochete Borrelia hermsii, a relapsing fever agent, evades the host's immune response through multiphasic antigenic variation. Antigen switching results from sequential expression of genes for serotype-specific outer membrane proteins known as variable major proteins (Vmp's); of the 25 serotypes that have been identified for the HS1 strain, serotypes 7 and 21 have been studied in greatest detail. In the present study, an atypical variant was predominant in the relapse from a serotype 21 infection in mice; relapse cells were bound by monoclonal antibodies specific for Vmp21 as well as antibodies specific for Vmp7. In Western blots (immunoblots), the variant had a single Vmp that was reactive with monoclonal antibodies representing both serotypes. The gene encoding this Vmp, vmp7/21, was cloned and characterized by restriction mapping and sequence analysis to determine the likely recombination event. Whereas the 5' end of vmp7/21 was identical to that of vmp21, its 3' end and flanking sequences were identical to the 3' end of vmp7. Unlike other vmp genes examined thus far, the vmp7/21 gene existed only in an expressed form; a silent, storage form of the gene was not detected. We conclude that the vmp7/21 gene was created by an intragenic recombination between the formerly expressed vmp21 gene and a silent vmp7 gene. This finding suggests that the lack of cross-reactivity between variants, which is usually observed, results from immunoselection against variants possessing chimeric Vmp's rather than from a switching mechanism that excludes partial gene replacements.

Full text

PDF
2516

Images in this article

2518Image
on p.2518
2518Image
on p.2518
2519Image
on p.2519

Selected References

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

  1. Anderson R. E., Warner N. L. Ionizing radiation and the immune response. Adv Immunol. 1976;24:215–335. doi: 10.1016/s0065-2776(08)60331-4. [DOI] [PubMed] [Google Scholar]
  2. Barbour A. G. Antigenic variation of a relapsing fever Borrelia species. Annu Rev Microbiol. 1990;44:155–171. doi: 10.1146/annurev.mi.44.100190.001103. [DOI] [PubMed] [Google Scholar]
  3. Barbour A. G. Antigenic variation of surface proteins of Borrelia species. Rev Infect Dis. 1988 Jul-Aug;10 (Suppl 2):S399–S402. doi: 10.1093/cid/10.supplement_2.s399. [DOI] [PubMed] [Google Scholar]
  4. Barbour A. G., Barrera O., Judd R. C. Structural analysis of the variable major proteins of Borrelia hermsii. J Exp Med. 1983 Dec 1;158(6):2127–2140. doi: 10.1084/jem.158.6.2127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barbour A. G., Burman N., Carter C. J., Kitten T., Bergström S. Variable antigen genes of the relapsing fever agent Borrelia hermsii are activated by promoter addition. Mol Microbiol. 1991 Feb;5(2):489–493. doi: 10.1111/j.1365-2958.1991.tb02132.x. [DOI] [PubMed] [Google Scholar]
  6. Barbour A. G., Garon C. F. Linear plasmids of the bacterium Borrelia burgdorferi have covalently closed ends. Science. 1987 Jul 24;237(4813):409–411. doi: 10.1126/science.3603026. [DOI] [PubMed] [Google Scholar]
  7. Barbour A. G., Garon C. F. The genes encoding major surface proteins of Borrelia burgdorferi are located on a plasmid. Ann N Y Acad Sci. 1988;539:144–153. doi: 10.1111/j.1749-6632.1988.tb31847.x. [DOI] [PubMed] [Google Scholar]
  8. Barbour A. G., Hayes S. F. Biology of Borrelia species. Microbiol Rev. 1986 Dec;50(4):381–400. doi: 10.1128/mr.50.4.381-400.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Barbour A. G., Hayes S. F., Heiland R. A., Schrumpf M. E., Tessier S. L. A Borrelia-specific monoclonal antibody binds to a flagellar epitope. Infect Immun. 1986 May;52(2):549–554. doi: 10.1128/iai.52.2.549-554.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Barbour A. G. Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med. 1984 Jul-Aug;57(4):521–525. [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Baroudy B. M., Venkatesan S., Moss B. Incompletely base-paired flip-flop terminal loops link the two DNA strands of the vaccinia virus genome into one uninterrupted polynucleotide chain. Cell. 1982 Feb;28(2):315–324. doi: 10.1016/0092-8674(82)90349-x. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Borst P. Molecular genetics of antigenic variation. Immunol Today. 1991 Mar;12(3):A29–A33. doi: 10.1016/S0167-5699(05)80009-X. [DOI] [PubMed] [Google Scholar]
  15. Burman N., Bergström S., Restrepo B. I., Barbour A. G. 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. 1990 Oct;4(10):1715–1726. doi: 10.1111/j.1365-2958.1990.tb00549.x. [DOI] [PubMed] [Google Scholar]
  16. Chen E. Y., Seeburg P. H. Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985 Apr;4(2):165–170. doi: 10.1089/dna.1985.4.165. [DOI] [PubMed] [Google Scholar]
  17. Cross G. A. Cellular and genetic aspects of antigenic variation in trypanosomes. Annu Rev Immunol. 1990;8:83–110. doi: 10.1146/annurev.iy.08.040190.000503. [DOI] [PubMed] [Google Scholar]
  18. Hinnebusch J., Bergström S., Barbour A. G. Cloning and sequence analysis of linear plasmid telomeres of the bacterium Borrelia burgdorferi. Mol Microbiol. 1990 May;4(5):811–820. doi: 10.1111/j.1365-2958.1990.tb00651.x. [DOI] [PubMed] [Google Scholar]
  19. Innis M. A., Myambo K. B., Gelfand D. H., Brow M. A. DNA sequencing with Thermus aquaticus DNA polymerase and direct sequencing of polymerase chain reaction-amplified DNA. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9436–9440. doi: 10.1073/pnas.85.24.9436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kitten T., Barbour A. G. Juxtaposition of expressed variable antigen genes with a conserved telomere in the bacterium Borrelia hermsii. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6077–6081. doi: 10.1073/pnas.87.16.6077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Klar A. J., McIndoo J., Strathern J. N., Hicks J. B. Evidence for a physical interaction between the transposed and the substituted sequences during mating type gene transposition in yeast. Cell. 1980 Nov;22(1 Pt 1):291–298. doi: 10.1016/0092-8674(80)90176-2. [DOI] [PubMed] [Google Scholar]
  22. Lee S. K., Woodland R. T. Selective effect of irradiation on responses to thymus-independent antigen. J Immunol. 1985 Feb;134(2):761–764. [PubMed] [Google Scholar]
  23. Meier J. T., Simon M. I., Barbour A. G. Antigenic variation is associated with DNA rearrangements in a relapsing fever Borrelia. Cell. 1985 Jun;41(2):403–409. doi: 10.1016/s0092-8674(85)80013-1. [DOI] [PubMed] [Google Scholar]
  24. Newman K., Jr, Johnson R. C. T-cell-independent elimination of Borrelia turicatae. Infect Immun. 1984 Sep;45(3):572–576. doi: 10.1128/iai.45.3.572-576.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Paster B. J., Dewhirst F. E., Weisburg W. G., Tordoff L. A., Fraser G. J., Hespell R. B., Stanton T. B., Zablen L., Mandelco L., Woese C. R. Phylogenetic analysis of the spirochetes. J Bacteriol. 1991 Oct;173(19):6101–6109. doi: 10.1128/jb.173.19.6101-6109.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pays E. Pseudogenes, chimaeric genes and the timing of antigen variation in African trypanosomes. Trends Genet. 1989 Dec;5(12):389–391. doi: 10.1016/0168-9525(89)90181-9. [DOI] [PubMed] [Google Scholar]
  27. Plasterk R. H., Simon M. I., Barbour A. G. Transposition of structural genes to an expression sequence on a linear plasmid causes antigenic variation in the bacterium Borrelia hermsii. Nature. 1985 Nov 21;318(6043):257–263. doi: 10.1038/318257a0. [DOI] [PubMed] [Google Scholar]
  28. Restrepo B. I., Kitten T., Carter C. J., Infante D., Barbour A. G. Subtelomeric expression regions of Borrelia hermsii linear plasmids are highly polymorphic. Mol Microbiol. 1992 Nov;6(22):3299–3311. doi: 10.1111/j.1365-2958.1992.tb02198.x. [DOI] [PubMed] [Google Scholar]
  29. Roth C., Bringaud F., Layden R. E., Baltz T., Eisen H. Active late-appearing variable surface antigen genes in Trypanosoma equiperdum are constructed entirely from pseudogenes. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9375–9379. doi: 10.1073/pnas.86.23.9375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Smith H. O., Birnstiel M. L. A simple method for DNA restriction site mapping. Nucleic Acids Res. 1976 Sep;3(9):2387–2398. doi: 10.1093/nar/3.9.2387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stoenner H. G., Dodd T., Larsen C. Antigenic variation of Borrelia hermsii. J Exp Med. 1982 Nov 1;156(5):1297–1311. doi: 10.1084/jem.156.5.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Strathern J. N., Klar A. J., Hicks J. B., Abraham J. A., Ivy J. M., Nasmyth K. A., McGill C. Homothallic switching of yeast mating type cassettes is initiated by a double-stranded cut in the MAT locus. Cell. 1982 Nov;31(1):183–192. doi: 10.1016/0092-8674(82)90418-4. [DOI] [PubMed] [Google Scholar]
  33. Thon G., Baltz T., Eisen H. Antigenic diversity by the recombination of pseudogenes. Genes Dev. 1989 Aug;3(8):1247–1254. doi: 10.1101/gad.3.8.1247. [DOI] [PubMed] [Google Scholar]
  34. Thon G., Baltz T., Giroud C., Eisen H. Trypanosome variable surface glycoproteins: composite genes and order of expression. Genes Dev. 1990 Aug;4(8):1374–1383. doi: 10.1101/gad.4.8.1374. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES