Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Jul;65(7):2992–2995. doi: 10.1128/iai.65.7.2992-2995.1997

FlaA, a putative flagellar outer sheath protein, is not an immunodominant antigen associated with Lyme disease.

Y Ge 1, N W Charon 1
PMCID: PMC175421  PMID: 9199479

Abstract

FlaA was recently found to be associated with flagellar filaments of Borrelia burgdorferi. We tested whether antibodies to this protein are a good indicator of infection, as antibodies to FlaA proteins in other spirochetal infections show an increase in titer. Although overproduction of intact FlaA was highly toxic to Escherichia coli, truncated proteins which lacked the N-terminal signal sequence could be successfully overexpressed. Immunoblotting with sera from mammalian hosts infected with B. burgdorferi indicated that FlaA is not an immunodominant antigen in Lyme disease. However, sera from two patients reacted with both recombinant and native FlaA protein, suggesting that B. burgdorferi FlaA was antigenic and expressed in vivo.

Full Text

The Full Text of this article is available as a PDF (394.4 KB).

Selected References

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

  1. Assous M. V., Postic D., Paul G., Névot P., Baranton G. Western blot analysis of sera from Lyme borreliosis patients according to the genomic species of the Borrelia strains used as antigens. Eur J Clin Microbiol Infect Dis. 1993 Apr;12(4):261–268. doi: 10.1007/BF01967256. [DOI] [PubMed] [Google Scholar]
  2. Baker-Zander S. A., Hook E. W., 3rd, Bonin P., Handsfield H. H., Lukehart S. A. Antigens of Treponema pallidum recognized by IgG and IgM antibodies during syphilis in humans. J Infect Dis. 1985 Feb;151(2):264–272. doi: 10.1093/infdis/151.2.264. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Blanco D. R., Champion C. I., Miller J. N., Lovett M. A. Antigenic and structural characterization of Treponema pallidum (Nichols strain) endoflagella. Infect Immun. 1988 Jan;56(1):168–175. doi: 10.1128/iai.56.1.168-175.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brahamsha B., Greenberg E. P. Biochemical and cytological analysis of the complex periplasmic flagella from Spirochaeta aurantia. J Bacteriol. 1988 Sep;170(9):4023–4032. doi: 10.1128/jb.170.9.4023-4032.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chapman A. J., Adler B., Faine S. Antigens recognised by the human immune response to infection with Leptospira interrogans serovar hardjo. J Med Microbiol. 1988 Apr;25(4):269–278. doi: 10.1099/00222615-25-4-269. [DOI] [PubMed] [Google Scholar]
  7. Charon N. W., Greenberg E. P., Koopman M. B., Limberger R. J. Spirochete chemotaxis, motility, and the structure of the spirochetal periplasmic flagella. Res Microbiol. 1992 Jul-Aug;143(6):597–603. doi: 10.1016/0923-2508(92)90117-7. [DOI] [PubMed] [Google Scholar]
  8. Coleman J. L., Benach J. L. Identification and characterization of an endoflagellar antigen of Borrelia burgdorferi. J Clin Invest. 1989 Jul;84(1):322–330. doi: 10.1172/JCI114157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Craft J. E., Fischer D. K., Shimamoto G. T., Steere A. C. Antigens of Borrelia burgdorferi recognized during Lyme disease. Appearance of a new immunoglobulin M response and expansion of the immunoglobulin G response late in the illness. J Clin Invest. 1986 Oct;78(4):934–939. doi: 10.1172/JCI112683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dalessio J., Ashley R. Highly sensitive enhanced chemiluminescence immunodetection method for herpes simplex virus type 2 Western immunoblot. J Clin Microbiol. 1992 Apr;30(4):1005–1007. doi: 10.1128/jcm.30.4.1005-1007.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fikrig E., Barthold S. W., Marcantonio N., Deponte K., Kantor F. S., Flavell R. A. Roles of OspA, OspB, and flagellin in protective immunity to Lyme borreliosis in laboratory mice. Infect Immun. 1992 Feb;60(2):657–661. doi: 10.1128/iai.60.2.657-661.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gassmann G. S., Jacobs E., Deutzmann R., Göbel U. B. Analysis of the Borrelia burgdorferi GeHo fla gene and antigenic characterization of its gene product. J Bacteriol. 1991 Feb;173(4):1452–1459. doi: 10.1128/jb.173.4.1452-1459.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ge Y., Charon N. W. An unexpected flaA homolog is present and expressed in Borrelia burgdorferi. J Bacteriol. 1997 Jan;179(2):552–556. doi: 10.1128/jb.179.2.552-556.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ge Y., Old I. G., Saint Girons I., Charon N. W. Molecular characterization of a large Borrelia burgdorferi motility operon which is initiated by a consensus sigma70 promoter. J Bacteriol. 1997 Apr;179(7):2289–2299. doi: 10.1128/jb.179.7.2289-2299.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goldstein S. F., Buttle K. F., Charon N. W. Structural analysis of the Leptospiraceae and Borrelia burgdorferi by high-voltage electron microscopy. J Bacteriol. 1996 Nov;178(22):6539–6545. doi: 10.1128/jb.178.22.6539-6545.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hanff P. A., Fehniger T. E., Miller J. N., Lovett M. A. Humoral immune response in human syphilis to polypeptides of Treponema pallidum. J Immunol. 1982 Sep;129(3):1287–1291. [PubMed] [Google Scholar]
  17. Hughes C. A., Engstrom S. M., Coleman L. A., Kodner C. B., Johnson R. C. Protective immunity is induced by a Borrelia burgdorferi mutant that lacks OspA and OspB. Infect Immun. 1993 Dec;61(12):5115–5122. doi: 10.1128/iai.61.12.5115-5122.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Isaacs R. D., Radolf J. D. Expression in Escherichia coli of the 37-kilodalton endoflagellar sheath protein of Treponema pallidum by use of the polymerase chain reaction and a T7 expression system. Infect Immun. 1990 Jul;58(7):2025–2034. doi: 10.1128/iai.58.7.2025-2034.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Johnson B. J., Robbins K. E., Bailey R. E., Cao B. L., Sviat S. L., Craven R. B., Mayer L. W., Dennis D. T. Serodiagnosis of Lyme disease: accuracy of a two-step approach using a flagella-based ELISA and immunoblotting. J Infect Dis. 1996 Aug;174(2):346–353. doi: 10.1093/infdis/174.2.346. [DOI] [PubMed] [Google Scholar]
  20. Kelson J. S., Adler B., Chapman A. J., Faine S. Identification of leptospiral flagellar antigens by gel electrophoresis and immunoblotting. J Med Microbiol. 1988 May;26(1):47–53. doi: 10.1099/00222615-26-1-47. [DOI] [PubMed] [Google Scholar]
  21. Kent K. A., Sellwood R., Lemcke R. M., Burrows M. R., Lysons R. J. Analysis of the axial filaments of Treponema hyodysenteriae by SDS-PAGE and immunoblotting. J Gen Microbiol. 1989 Jun;135(6):1625–1632. doi: 10.1099/00221287-135-6-1625. [DOI] [PubMed] [Google Scholar]
  22. Koopman M. B., Baats E., de Leeuw O. S., van der Zeijst B. A., Kusters J. G. Molecular analysis of a flagellar core protein gene of Serpulina (Treponema) hyodysenteriae. J Gen Microbiol. 1993 Aug;139(8):1701–1706. doi: 10.1099/00221287-139-8-1701. [DOI] [PubMed] [Google Scholar]
  23. Koopman M. B., Baats E., van Vorstenbosch C. J., van der Zeijst B. A., Kusters J. G. The periplasmic flagella of Serpulina (Treponema) hyodysenteriae are composed of two sheath proteins and three core proteins. J Gen Microbiol. 1992 Dec;138(12):2697–2706. doi: 10.1099/00221287-138-12-2697. [DOI] [PubMed] [Google Scholar]
  24. Li Z., Dumas F., Dubreuil D., Jacques M. A species-specific periplasmic flagellar protein of Serpulina (Treponema) hyodysenteriae. J Bacteriol. 1993 Dec;175(24):8000–8007. doi: 10.1128/jb.175.24.8000-8007.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Limberger R. J., Charon N. W. Antiserum to the 33,000-dalton periplasmic-flagellum protein of "Treponema phagedenis" reacts with other treponemes and Spirochaeta aurantia. J Bacteriol. 1986 Nov;168(2):1030–1032. doi: 10.1128/jb.168.2.1030-1032.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Magnarelli L. A. Current status of laboratory diagnosis for Lyme disease. Am J Med. 1995 Apr 24;98(4A):10S–14S. doi: 10.1016/s0002-9343(99)80039-4. [DOI] [PubMed] [Google Scholar]
  27. Magnarelli L. A., Fikrig E., Berland R., Anderson J. F., Flavell R. A. Comparison of whole-cell antibodies and an antigenic flagellar epitope of Borrelia burgdorferi in serologic tests for diagnosis of Lyme borreliosis. J Clin Microbiol. 1992 Dec;30(12):3158–3162. doi: 10.1128/jcm.30.12.3158-3162.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Magnarelli L. A., Fikrig E., Padula S. J., Anderson J. F., Flavell R. A. Use of recombinant antigens of Borrelia burgdorferi in serologic tests for diagnosis of lyme borreliosis. J Clin Microbiol. 1996 Feb;34(2):237–240. doi: 10.1128/jcm.34.2.237-240.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Moskophidis M., Müller F. Molecular analysis of immunoglobulins M and G immune response to protein antigens of Treponema pallidum in human syphilis. Infect Immun. 1984 Jan;43(1):127–132. doi: 10.1128/iai.43.1.127-132.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Norris S. J. Polypeptides of Treponema pallidum: progress toward understanding their structural, functional, and immunologic roles. Treponema Pallidum Polypeptide Research Group. Microbiol Rev. 1993 Sep;57(3):750–779. doi: 10.1128/mr.57.3.750-779.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pedersen N. S., Petersen C. S., Axelsen N. H. Enzyme-linked immunosorbent assay for detection of immunoglobulin M antibody against the Reiter treponeme flagellum in syphilis. J Clin Microbiol. 1982 Oct;16(4):608–614. doi: 10.1128/jcm.16.4.608-614.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pedersen N. S., Petersen C. S., Vejtorp M., Axelsen N. H. Serodiagnosis of syphilis by an enzyme-linked immunosorbent assay for IgG antibodies against the Reiter treponeme flagellum. Scand J Immunol. 1982 Apr;15(4):341–348. doi: 10.1111/j.1365-3083.1982.tb00657.x. [DOI] [PubMed] [Google Scholar]
  33. Roberts E. D., Bohm R. P., Jr, Cogswell F. B., Lanners H. N., Lowrie R. C., Jr, Povinelli L., Piesman J., Philipp M. T. Chronic lyme disease in the rhesus monkey. Lab Invest. 1995 Feb;72(2):146–160. [PubMed] [Google Scholar]
  34. Sadziene A., Thomas D. D., Bundoc V. G., Holt S. C., Barbour A. G. A flagella-less mutant of Borrelia burgdorferi. Structural, molecular, and in vitro functional characterization. J Clin Invest. 1991 Jul;88(1):82–92. doi: 10.1172/JCI115308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Suk K., Das S., Sun W., Jwang B., Barthold S. W., Flavell R. A., Fikrig E. Borrelia burgdorferi genes selectively expressed in the infected host. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4269–4273. doi: 10.1073/pnas.92.10.4269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Szczepanski A., Benach J. L. Lyme borreliosis: host responses to Borrelia burgdorferi. Microbiol Rev. 1991 Mar;55(1):21–34. doi: 10.1128/mr.55.1.21-34.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Trueba G. A., Bolin C. A., Zuerner R. L. Characterization of the periplasmic flagellum proteins of Leptospira interrogans. J Bacteriol. 1992 Jul;174(14):4761–4768. doi: 10.1128/jb.174.14.4761-4768.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wilson D. R., Beveridge T. J. Bacterial flagellar filaments and their component flagellins. Can J Microbiol. 1993 May;39(5):451–472. doi: 10.1139/m93-066. [DOI] [PubMed] [Google Scholar]

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

RESOURCES