Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Jan;64(1):262–268. doi: 10.1128/iai.64.1.262-268.1996

A glyceraldehyde-3-phosphate dehydrogenase homolog in Borrelia burgdorferi and Borrelia hermsii.

P Anda 1, J A Gebbia 1, P B Backenson 1, J L Coleman 1, J L Benach 1
PMCID: PMC173754  PMID: 8557349

Abstract

A polyreactive monoclonal antibody recognized a 38.5-kDa polypeptide with amino-terminal sequence identity to conserved regions of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in Borrelia burgdorferi, the Lyme disease agent, and Borrelia hermsii, an agent of American relapsing fever. This monoclonal antibody also recognized GAPDH from other pathogenic spirochetes and other prokaryotes and eukaryotes as well. GAPDH activity was detected in sonicates of both B. burgdorferi and B. hermsii but not in live, intact organisms, indicating the possibility of a subsurface localization for the Borrelia GAPDH activity. Degenerate primers constructed from highly conserved regions of gapdh of other prokaryotes successfully amplified this gene homolog in both B. burgdorferi and B. hermsii. Nuclei acid and deduced amino acid sequence analysis of the 838-bp probes for each borrelia indicated 93.9% identity between B. burgdorferi and B. hermsii at the amino acid level. Amino acid identities of B. burgdorferi and B. hermsii with Bacillus stearothermophilus were 59.2% and 58.8% respectively. Southern hybridization studies indicated that the gene encoding GAPDH is located on the chromosome of each borrella. In other bacterial species, GAPDH has other functions in addition to its traditional enzymatic role in the glycolytic pathway. GAPDH may play a similar role in borrelias.

Full Text

The Full Text of this article is available as a PDF (317.7 KB).

Selected References

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

  1. Alefounder P. R., Perham R. N. Identification, molecular cloning and sequence analysis of a gene cluster encoding the class II fructose 1,6-bisphosphate aldolase, 3-phosphoglycerate kinase and a putative second glyceraldehyde 3-phosphate dehydrogenase of Escherichia coli. Mol Microbiol. 1989 Jun;3(6):723–732. doi: 10.1111/j.1365-2958.1989.tb00221.x. [DOI] [PubMed] [Google Scholar]
  2. Anda P., Backenson P. B., Coleman J. L., Benach J. L. Epitopes shared by unrelated antigens of Borrelia burgdorferi. Infect Immun. 1994 Mar;62(3):1070–1078. doi: 10.1128/iai.62.3.1070-1078.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anzola J., Luft B. J., Gorgone G., Dattwyler R. J., Soderberg C., Lahesmaa R., Peltz G. Borrelia burgdorferi HSP70 homolog: characterization of an immunoreactive stress protein. Infect Immun. 1992 Sep;60(9):3704–3713. doi: 10.1128/iai.60.9.3704-3713.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benach J. L., Bosler E. M., Hanrahan J. P., Coleman J. L., Habicht G. S., Bast T. F., Cameron D. J., Ziegler J. L., Barbour A. G., Burgdorfer W. Spirochetes isolated from the blood of two patients with Lyme disease. N Engl J Med. 1983 Mar 31;308(13):740–742. doi: 10.1056/NEJM198303313081302. [DOI] [PubMed] [Google Scholar]
  5. Bergström S., Bundoc V. G., Barbour A. G. Molecular analysis of linear plasmid-encoded major surface proteins, OspA and OspB, of the Lyme disease spirochaete Borrelia burgdorferi. Mol Microbiol. 1989 Apr;3(4):479–486. doi: 10.1111/j.1365-2958.1989.tb00194.x. [DOI] [PubMed] [Google Scholar]
  6. Biesecker G., Harris J. I., Thierry J. C., Walker J. E., Wonacott A. J. Sequence and structure of D-glyceraldehyde 3-phosphate dehydrogenase from Bacillus stearothermophilus. Nature. 1977 Mar 24;266(5600):328–333. doi: 10.1038/266328a0. [DOI] [PubMed] [Google Scholar]
  7. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  8. Branlant G., Branlant C. Nucleotide sequence of the Escherichia coli gap gene. Different evolutionary behavior of the NAD+-binding domain and of the catalytic domain of D-glyceraldehyde-3-phosphate dehydrogenase. Eur J Biochem. 1985 Jul 1;150(1):61–66. doi: 10.1111/j.1432-1033.1985.tb08988.x. [DOI] [PubMed] [Google Scholar]
  9. Broder C. C., Lottenberg R., von Mering G. O., Johnston K. H., Boyle M. D. Isolation of a prokaryotic plasmin receptor. Relationship to a plasminogen activator produced by the same micro-organism. J Biol Chem. 1991 Mar 15;266(8):4922–4928. [PubMed] [Google Scholar]
  10. 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]
  11. Charrier-Ferrara S., Caillol D., Goudot-Crozel V. Complete sequence of the Schistosoma mansoni glyceraldehyde-3-phosphate dehydrogenase gene encoding a major surface antigen. Mol Biochem Parasitol. 1992 Dec;56(2):339–343. doi: 10.1016/0166-6851(92)90184-l. [DOI] [PubMed] [Google Scholar]
  12. Coleman J. L., Benach J. L. Isolation of antigenic components from the Lyme disease spirochete: their role in early diagnosis. J Infect Dis. 1987 Apr;155(4):756–765. doi: 10.1093/infdis/155.4.756. [DOI] [PubMed] [Google Scholar]
  13. Coleman J. L., Rogers R. C., Benach J. L. Selection of an escape variant of Borrelia burgdorferi by use of bactericidal monoclonal antibodies to OspB. Infect Immun. 1992 Aug;60(8):3098–3104. doi: 10.1128/iai.60.8.3098-3104.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Coleman J. L., Sellati T. J., Testa J. E., Kew R. R., Furie M. B., Benach J. L. Borrelia burgdorferi binds plasminogen, resulting in enhanced penetration of endothelial monolayers. Infect Immun. 1995 Jul;63(7):2478–2484. doi: 10.1128/iai.63.7.2478-2484.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dugaiczyk A., Haron J. A., Stone E. M., Dennison O. E., Rothblum K. N., Schwartz R. J. Cloning and sequencing of a deoxyribonucleic acid copy of glyceraldehyde-3-phosphate dehydrogenase messenger ribonucleic acid isolated from chicken muscle. Biochemistry. 1983 Mar 29;22(7):1605–1613. doi: 10.1021/bi00276a013. [DOI] [PubMed] [Google Scholar]
  16. Ercolani L., Florence B., Denaro M., Alexander M. Isolation and complete sequence of a functional human glyceraldehyde-3-phosphate dehydrogenase gene. J Biol Chem. 1988 Oct 25;263(30):15335–15341. [PubMed] [Google Scholar]
  17. Ferdinand W. The isolation and specific activity of rabbit-muscle glyceraldehyde phosphate dehydrogenase. Biochem J. 1964 Sep;92(3):578–585. doi: 10.1042/bj0920578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ferdows M. S., Barbour A. G. Megabase-sized linear DNA in the bacterium Borrelia burgdorferi, the Lyme disease agent. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5969–5973. doi: 10.1073/pnas.86.15.5969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fuchs H., Wallich R., Simon M. M., Kramer M. D. The outer surface protein A of the spirochete Borrelia burgdorferi is a plasmin(ogen) receptor. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12594–12598. doi: 10.1073/pnas.91.26.12594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hocking J. D., Harris J. I. D-glyceraldehyde-3-phosphate dehydrogenase. Amino-acid sequence of the enzyme from the extreme thermophile Thermus aquaticus. Eur J Biochem. 1980 Jul;108(2):567–579. doi: 10.1111/j.1432-1033.1980.tb04752.x. [DOI] [PubMed] [Google Scholar]
  21. Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Huitorel P., Pantaloni D. Bundling of microtubules by glyceraldehyde-3-phosphate dehydrogenase and its modulation by ATP. Eur J Biochem. 1985 Jul 15;150(2):265–269. doi: 10.1111/j.1432-1033.1985.tb09016.x. [DOI] [PubMed] [Google Scholar]
  23. Kemp B. E., Pearson R. B. Protein kinase recognition sequence motifs. Trends Biochem Sci. 1990 Sep;15(9):342–346. doi: 10.1016/0968-0004(90)90073-k. [DOI] [PubMed] [Google Scholar]
  24. Klempner M. S., Noring R., Epstein M. P., McCloud B., Hu R., Limentani S. A., Rogers R. A. Binding of human plasminogen and urokinase-type plasminogen activator to the Lyme disease spirochete, Borrelia burgdorferi. J Infect Dis. 1995 May;171(5):1258–1265. doi: 10.1093/infdis/171.5.1258. [DOI] [PubMed] [Google Scholar]
  25. Kliman H. J., Steck T. L. Association of glyceraldehyde-3-phosphate dehydrogenase with the human red cell membrane. A kinetic analysis. J Biol Chem. 1980 Jul 10;255(13):6314–6321. [PubMed] [Google Scholar]
  26. Laemmli U. K., Favre M. Maturation of the head of bacteriophage T4. I. DNA packaging events. J Mol Biol. 1973 Nov 15;80(4):575–599. doi: 10.1016/0022-2836(73)90198-8. [DOI] [PubMed] [Google Scholar]
  27. Lefebvre R. B., Perng G. C., Johnson R. C. The 83-kilodalton antigen of Borrelia burgdorferi which stimulates immunoglobulin M (IgM) and IgG responses in infected hosts is expressed by a chromosomal gene. J Clin Microbiol. 1990 Jul;28(7):1673–1675. doi: 10.1128/jcm.28.7.1673-1675.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Logtenberg T. Properties of polyreactive natural antibodies to self and foreign antigens. J Clin Immunol. 1990 May;10(3):137–140. doi: 10.1007/BF00917912. [DOI] [PubMed] [Google Scholar]
  29. Lottenberg R., Broder C. C., Boyle M. D. Identification of a specific receptor for plasmin on a group A streptococcus. Infect Immun. 1987 Aug;55(8):1914–1918. doi: 10.1128/iai.55.8.1914-1918.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lottenberg R., Broder C. C., Boyle M. D., Kain S. J., Schroeder B. L., Curtiss R., 3rd Cloning, sequence analysis, and expression in Escherichia coli of a streptococcal plasmin receptor. J Bacteriol. 1992 Aug;174(16):5204–5210. doi: 10.1128/jb.174.16.5204-5210.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Markos A., Miretsky A., Müller M. A glyceraldehyde-3-phosphate dehydrogenase with eubacterial features in the amitochondriate eukaryote, Trichomonas vaginalis. J Mol Evol. 1993 Dec;37(6):631–643. doi: 10.1007/BF00182749. [DOI] [PubMed] [Google Scholar]
  32. Matsudaira P. Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes. J Biol Chem. 1987 Jul 25;262(21):10035–10038. [PubMed] [Google Scholar]
  33. Meunier J. C., Dalziel K. Kinetic studies of glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle. Eur J Biochem. 1978 Jan 16;82(2):483–492. doi: 10.1111/j.1432-1033.1978.tb12042.x. [DOI] [PubMed] [Google Scholar]
  34. Meyer-Siegler K., Mauro D. J., Seal G., Wurzer J., deRiel J. K., Sirover M. A. A human nuclear uracil DNA glycosylase is the 37-kDa subunit of glyceraldehyde-3-phosphate dehydrogenase. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8460–8464. doi: 10.1073/pnas.88.19.8460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pancholi V., Fischetti V. A. A major surface protein on group A streptococci is a glyceraldehyde-3-phosphate-dehydrogenase with multiple binding activity. J Exp Med. 1992 Aug 1;176(2):415–426. doi: 10.1084/jem.176.2.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Pancholi V., Fischetti V. A. Glyceraldehyde-3-phosphate dehydrogenase on the surface of group A streptococci is also an ADP-ribosylating enzyme. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8154–8158. doi: 10.1073/pnas.90.17.8154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Perng G. C., LeFebvre R. B., Johnson R. C. Further characterization of a potent immunogen and the chromosomal gene encoding it in the Lyme disease agent, Borrelia burgdorferi. Infect Immun. 1991 Jun;59(6):2070–2074. doi: 10.1128/iai.59.6.2070-2074.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Perucho M., Salas J., Salas M. L. Identification of the mammalian DNA-binding protein P8 as glyceraldehyde-3-phosphate dehydrogenase. Eur J Biochem. 1977 Dec;81(3):557–562. doi: 10.1111/j.1432-1033.1977.tb11982.x. [DOI] [PubMed] [Google Scholar]
  39. Piechaczyk M., Blanchard J. M., Riaad-El Sabouty S., Dani C., Marty L., Jeanteur P. Unusual abundance of vertebrate 3-phosphate dehydrogenase pseudogenes. 1984 Nov 29-Dec 5Nature. 312(5993):469–471. doi: 10.1038/312469a0. [DOI] [PubMed] [Google Scholar]
  40. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Schläpfer B. S., Portmann W., Branlant C., Branlant G., Zuber H. Nucleotide sequence of the glyceraldehyde-3-phosphate dehydrogenase from Bacillus megaterium. Nucleic Acids Res. 1990 Nov 11;18(21):6422–6422. doi: 10.1093/nar/18.21.6422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Soukri A., Mougin A., Corbier C., Wonacott A., Branlant C., Branlant G. Role of the histidine 176 residue in glyceraldehyde-3-phosphate dehydrogenase as probed by site-directed mutagenesis. Biochemistry. 1989 Mar 21;28(6):2586–2592. doi: 10.1021/bi00432a036. [DOI] [PubMed] [Google Scholar]
  43. Steere A. C., Grodzicki R. L., Kornblatt A. N., Craft J. E., Barbour A. G., Burgdorfer W., Schmid G. P., Johnson E., Malawista S. E. The spirochetal etiology of Lyme disease. N Engl J Med. 1983 Mar 31;308(13):733–740. doi: 10.1056/NEJM198303313081301. [DOI] [PubMed] [Google Scholar]
  44. Stone E. M., Rothblum K. N., Alevy M. C., Kuo T. M., Schwartz R. J. Complete sequence of the chicken glyceraldehyde-3-phosphate dehydrogenase gene. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1628–1632. doi: 10.1073/pnas.82.6.1628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Ternynck T., Avrameas S. Murine natural monoclonal autoantibodies: a study of their polyspecificities and their affinities. Immunol Rev. 1986 Dec;94:99–112. doi: 10.1111/j.1600-065x.1986.tb01166.x. [DOI] [PubMed] [Google Scholar]
  46. Tilly K., Hauser R., Campbell J., Ostheimer G. J. Isolation of dnaJ, dnaK, and grpE homologues from Borrelia burgdorferi and complementation of Escherichia coli mutants. Mol Microbiol. 1993 Feb;7(3):359–369. doi: 10.1111/j.1365-2958.1993.tb01128.x. [DOI] [PubMed] [Google Scholar]
  47. Tsai I. H., Murthy S. N., Steck T. L. Effect of red cell membrane binding on the catalytic activity of glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem. 1982 Feb 10;257(3):1438–1442. [PubMed] [Google Scholar]

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

RESOURCES