Skip to main content
NCBI home page
Journal of Clinical Microbiology logoLink to Journal of Clinical Microbiology
. 1996 Oct;34(10):2483–2492. doi: 10.1128/jcm.34.10.2483-2492.1996

GlpQ: an antigen for serological discrimination between relapsing fever and Lyme borreliosis.

T G Schwan 1, M E Schrumpf 1, B J Hinnebusch 1, D E Anderson Jr 1, M E Konkel 1
PMCID: PMC229300  PMID: 8880505

Abstract

Tick-borne relapsing fever is caused by numerous Borrelia species maintained in nature by Ornithodoros tick-mammal cycles. Serological confirmation is based on either an immunofluorescence assay or an enzyme-linked immunosorbent assay using whole cells or sonicated Borrelia hermsii as the antigen. However, antigenic variability of this bacterium's outer surface proteins and antigens shared with the Lyme disease spirochete (B. burgdorferi), may cause both false-negative and false-positive results when testing sera of patients suspected to have either relapsing fever or Lyme disease. To develop a specific serological test for relapsing fever, we created a genomic DNA library of B. hermsii, screened transformed Escherichia coli cells for immunoreactivity with high-titered (> or = 1:2,048) human anti-B. hermsii antiserum, and selected an immunoreactive clone (pSPR75) expressing a 39-kDa protein. DNA sequencing, subcloning, and serum adsorption experiments identified the immunoreactive protein as a homolog of GlpQ, a glycerophosphodiester phosphodiesterase identified previously in E. coli, Haemophilus influenzae, and Bacillus subtilis. Serum samples from humans and mice infected with B. hermsii or other species of relapsing fever spirochetes contained antibodies recognizing GlpQ, whereas serum samples from Lyme disease and syphilis patients were nonreactive. Serologic tests based on this antigen will identify people exposed previously to relapsing fever spirochetes and help clarify the distribution of relapsing fever and Lyme disease in situations in which the occurrence of their causative agents is uncertain.

Full Text

The Full Text of this article is available as a PDF (474.5 KB).

Selected References

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

  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Anda P., Gebbia J. A., Backenson P. B., Coleman J. L., Benach J. L. A glyceraldehyde-3-phosphate dehydrogenase homolog in Borrelia burgdorferi and Borrelia hermsii. Infect Immun. 1996 Jan;64(1):262–268. doi: 10.1128/iai.64.1.262-268.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BURGDORFER W. Analyse des Infektionsverlaufes bei Ornithodorus moubata (Murray) und der natürlichen Uebertragung von Spirochaeta duttoni. Acta Trop. 1951;8(3):193–262. [PubMed] [Google Scholar]
  4. Barbour A. G., Fish D. The biological and social phenomenon of Lyme disease. Science. 1993 Jun 11;260(5114):1610–1616. doi: 10.1126/science.8503006. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Barbour A. G. Immunobiology of relapsing fever. Contrib Microbiol Immunol. 1987;8:125–137. [PubMed] [Google Scholar]
  7. 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]
  8. Barbour A. G. Laboratory aspects of Lyme borreliosis. Clin Microbiol Rev. 1988 Oct;1(4):399–414. doi: 10.1128/cmr.1.4.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Barbour A. G., Tessier S. L., Hayes S. F. Variation in a major surface protein of Lyme disease spirochetes. Infect Immun. 1984 Jul;45(1):94–100. doi: 10.1128/iai.45.1.94-100.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Borgnolo G., Hailu B., Chiabrera F. Louse-borne relapsing fever in Ethiopia. Lancet. 1991 Sep 28;338(8770):827–827. doi: 10.1016/0140-6736(91)90721-z. [DOI] [PubMed] [Google Scholar]
  11. Borgnolo G., Hailu B., Ciancarelli A., Almaviva M., Woldemariam T. Louse-borne relapsing fever. A clinical and an epidemiological study of 389 patients in Asella Hospital, Ethiopia. Trop Geogr Med. 1993;45(2):66–69. [PubMed] [Google Scholar]
  12. Boyer K. M., Munford R. S., Maupin G. O., Pattison C. P., Fox M. D., Barnes A. M., Jones W. L., Maynard J. E. Tick-borne relapsing fever: an interstate outbreak originating at Grand Canyon National Park. Am J Epidemiol. 1977 May;105(5):469–479. doi: 10.1093/oxfordjournals.aje.a112406. [DOI] [PubMed] [Google Scholar]
  13. Breitschwerdt E. B., Nicholson W. L., Kiehl A. R., Steers C., Meuten D. J., Levine J. F. Natural infections with Borrelia spirochetes in two dogs from Florida. J Clin Microbiol. 1994 Feb;32(2):352–357. doi: 10.1128/jcm.32.2.352-357.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Burgdorfer W., Barbour A. G., Hayes S. F., Benach J. L., Grunwaldt E., Davis J. P. Lyme disease-a tick-borne spirochetosis? Science. 1982 Jun 18;216(4552):1317–1319. doi: 10.1126/science.7043737. [DOI] [PubMed] [Google Scholar]
  15. Craft J. E., Grodzicki R. L., Steere A. C. Antibody response in Lyme disease: evaluation of diagnostic tests. J Infect Dis. 1984 May;149(5):789–795. doi: 10.1093/infdis/149.5.789. [DOI] [PubMed] [Google Scholar]
  16. Eiglmeier K., Boos W., Cole S. T. Nucleotide sequence and transcriptional startpoint of the glpT gene of Escherichia coli: extensive sequence homology of the glycerol-3-phosphate transport protein with components of the hexose-6-phosphate transport system. Mol Microbiol. 1987 Nov;1(3):251–258. doi: 10.1111/j.1365-2958.1987.tb01931.x. [DOI] [PubMed] [Google Scholar]
  17. Higgins D. G., Bleasby A. J., Fuchs R. CLUSTAL V: improved software for multiple sequence alignment. Comput Appl Biosci. 1992 Apr;8(2):189–191. doi: 10.1093/bioinformatics/8.2.189. [DOI] [PubMed] [Google Scholar]
  18. Janson H., Hedén L. O., Grubb A., Ruan M. R., Forsgren A. Protein D, an immunoglobulin D-binding protein of Haemophilus influenzae: cloning, nucleotide sequence, and expression in Escherichia coli. Infect Immun. 1991 Jan;59(1):119–125. doi: 10.1128/iai.59.1.119-125.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kawabata H., Masuzawa T., Yanagihara Y. Genomic analysis of Borrelia japonica sp. nov. isolated from Ixodes ovatus in Japan. Microbiol Immunol. 1993;37(11):843–848. doi: 10.1111/j.1348-0421.1993.tb01714.x. [DOI] [PubMed] [Google Scholar]
  20. Kelly R. Cultivation of Borrelia hermsi. Science. 1971 Jul 30;173(3995):443–444. doi: 10.1126/science.173.3995.443. [DOI] [PubMed] [Google Scholar]
  21. Kurashige S., Bissett M., Oshiro L. Characterization of a tick isolate of Borrelia burgdorferi that possesses a major low-molecular-weight surface protein. J Clin Microbiol. 1990 Jun;28(6):1362–1366. doi: 10.1128/jcm.28.6.1362-1366.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  23. Lane R. S., Burgdorfer W., Hayes S. F., Barbour A. G. Isolation of a spirochete from the soft tick, Ornithodoros coriaceus: a possible agent of epizootic bovine abortion. Science. 1985 Oct 4;230(4721):85–87. doi: 10.1126/science.3898367. [DOI] [PubMed] [Google Scholar]
  24. Larson T. J., Ehrmann M., Boos W. Periplasmic glycerophosphodiester phosphodiesterase of Escherichia coli, a new enzyme of the glp regulon. J Biol Chem. 1983 May 10;258(9):5428–5432. [PubMed] [Google Scholar]
  25. Magnarelli L. A., Anderson J. F., Barbour A. G. Enzyme-linked immunosorbent assays for Lyme disease: reactivity of subunits of Borrelia burgdorferi. J Infect Dis. 1989 Jan;159(1):43–49. doi: 10.1093/infdis/159.1.43. [DOI] [PubMed] [Google Scholar]
  26. Magnarelli L. A., Anderson J. F. Enzyme-linked immunosorbent assays for the detection of class-specific immunoglobulins to Borrelia burgdorferi. Am J Epidemiol. 1988 Apr;127(4):818–825. doi: 10.1093/oxfordjournals.aje.a114864. [DOI] [PubMed] [Google Scholar]
  27. Magnarelli L. A., Anderson J. F., Johnson R. C. Cross-reactivity in serological tests for Lyme disease and other spirochetal infections. J Infect Dis. 1987 Jul;156(1):183–188. doi: 10.1093/infdis/156.1.183. [DOI] [PubMed] [Google Scholar]
  28. Magnarelli L. A., Meegan J. M., Anderson J. F., Chappell W. A. Comparison of an indirect fluorescent-antibody test with an enzyme-linked immunosorbent assay for serological studies of Lyme disease. J Clin Microbiol. 1984 Aug;20(2):181–184. doi: 10.1128/jcm.20.2.181-184.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mullis K. B., Faloona F. A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. doi: 10.1016/0076-6879(87)55023-6. [DOI] [PubMed] [Google Scholar]
  30. Mullis K., Faloona F., Scharf S., Saiki R., Horn G., Erlich H. Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):263–273. doi: 10.1101/sqb.1986.051.01.032. [DOI] [PubMed] [Google Scholar]
  31. Munson R. S., Jr, Sasaki K. Protein D, a putative immunoglobulin D-binding protein produced by Haemophilus influenzae, is glycerophosphodiester phosphodiesterase. J Bacteriol. 1993 Jul;175(14):4569–4571. doi: 10.1128/jb.175.14.4569-4571.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nilsson R. P., Beijer L., Rutberg B. The glpT and glpQ genes of the glycerol regulon in Bacillus subtilis. Microbiology. 1994 Apr;140(Pt 4):723–730. doi: 10.1099/00221287-140-4-723. [DOI] [PubMed] [Google Scholar]
  33. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  34. Ormsbee R., Peacock M., Philip R., Casper E., Plorde J., Gabre-Kidan T., Wright L. Serologic diagnosis of epidemic typhus fever. Am J Epidemiol. 1977 Mar;105(3):261–271. doi: 10.1093/oxfordjournals.aje.a112382. [DOI] [PubMed] [Google Scholar]
  35. Rath P. M., Rögler G., Schönberg A., Pohle H. D., Fehrenbach F. J. Relapsing fever and its serological discrimination from Lyme borreliosis. Infection. 1992 Sep-Oct;20(5):283–286. doi: 10.1007/BF01710797. [DOI] [PubMed] [Google Scholar]
  36. Ruan M. R., Akkoyunlu M., Grubb A., Forsgren A. Protein D of Haemophilus influenzae. A novel bacterial surface protein with affinity for human IgD. J Immunol. 1990 Nov 15;145(10):3379–3384. [PubMed] [Google Scholar]
  37. Schwan T. G., Kime K. K., Schrumpf M. E., Coe J. E., Simpson W. J. Antibody response in white-footed mice (Peromyscus leucopus) experimentally infected with the Lyme disease spirochete (Borrelia burgdorferi). Infect Immun. 1989 Nov;57(11):3445–3451. doi: 10.1128/iai.57.11.3445-3451.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Simpson W. J., Burgdorfer W., Schrumpf M. E., Karstens R. H., Schwan T. G. Antibody to a 39-kilodalton Borrelia burgdorferi antigen (P39) as a marker for infection in experimentally and naturally inoculated animals. J Clin Microbiol. 1991 Feb;29(2):236–243. doi: 10.1128/jcm.29.2.236-243.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Simpson W. J., Garon C. F., Schwan T. G. Analysis of supercoiled circular plasmids in infectious and non-infectious Borrelia burgdorferi. Microb Pathog. 1990 Feb;8(2):109–118. doi: 10.1016/0882-4010(90)90075-2. [DOI] [PubMed] [Google Scholar]
  40. Simpson W. J., Schrumpf M. E., Schwan T. G. Reactivity of human Lyme borreliosis sera with a 39-kilodalton antigen specific to Borrelia burgdorferi. J Clin Microbiol. 1990 Jun;28(6):1329–1337. doi: 10.1128/jcm.28.6.1329-1337.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. Thompson R. S., Burgdorfer W., Russell R., Francis B. J. Outbreak of tick-borne relapsing fever in Spokane County, Washington. JAMA. 1969 Nov 10;210(6):1045–1050. [PubMed] [Google Scholar]
  43. Tommassen J., Eiglmeier K., Cole S. T., Overduin P., Larson T. J., Boos W. Characterization of two genes, glpQ and ugpQ, encoding glycerophosphoryl diester phosphodiesterases of Escherichia coli. Mol Gen Genet. 1991 Apr;226(1-2):321–327. doi: 10.1007/BF00273621. [DOI] [PubMed] [Google Scholar]
  44. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wu H. C., Tokunaga M. Biogenesis of lipoproteins in bacteria. Curr Top Microbiol Immunol. 1986;125:127–157. doi: 10.1007/978-3-642-71251-7_9. [DOI] [PubMed] [Google Scholar]
  46. Ye S. Z., Larson T. J. Structures of the promoter and operator of the glpD gene encoding aerobic sn-glycerol-3-phosphate dehydrogenase of Escherichia coli K-12. J Bacteriol. 1988 Sep;170(9):4209–4215. doi: 10.1128/jb.170.9.4209-4215.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES