Abstract
We have identified four loci in Borrelia burgdorferi B31 that contain open reading frames capable of encoding six proteins that are related to the antigenic proteins OspE and OspF. We have designated these proteins Erp, for OspEF-related protein, and named their respective genes erp. The erpA and erpB genes are linked, as are erpC and erpD, and the pairs probably constitute two operons. The erpG and erpH genes appear to be monocistronic. The ErpA and ErpC proteins are expressed by B. burgdorferi B31 in culture and are recognized by a polyclonal antiserum raised against the OspE protein of B. burgdorferi N40. The four erp loci are each located on different 32-kb circular plasmids that contain additional DNA sequences that are homologous to each other and to an 8.3-kb circular plasmid of B. burgdorferi sensu lato Ip2l. All four 32-kb plasmids can be maintained within a single bacterium, which may provide a model for the study of plasmid replication and segregation in B. burgdorferi.
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- Akins D. R., Porcella S. F., Popova T. G., Shevchenko D., Baker S. I., Li M., Norgard M. V., Radolf J. D. Evidence for in vivo but not in vitro expression of a Borrelia burgdorferi outer surface protein F (OspF) homologue. Mol Microbiol. 1995 Nov;18(3):507–520. doi: 10.1111/j.1365-2958.1995.mmi_18030507.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Amouriaux P., Assous M., Margarita D., Baranton G., Saint Girons I. Polymerase chain reaction with the 30-kb circular plasmid of Borrelia burgdorferi B31 as a target for detection of the Lyme borreliosis agents in cerebrospinal fluid. Res Microbiol. 1993 Mar-Apr;144(3):211–219. doi: 10.1016/0923-2508(93)90046-5. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Barbour A. G. Linear DNA of Borrelia species and antigenic variation. Trends Microbiol. 1993 Sep;1(6):236–239. doi: 10.1016/0966-842x(93)90139-i. [DOI] [PubMed] [Google Scholar]
- Barbour A. G. Plasmid analysis of Borrelia burgdorferi, the Lyme disease agent. J Clin Microbiol. 1988 Mar;26(3):475–478. doi: 10.1128/jcm.26.3.475-478.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barthold S. W., Moody K. D., Terwilliger G. A., Duray P. H., Jacoby R. O., Steere A. C. Experimental Lyme arthritis in rats infected with Borrelia burgdorferi. J Infect Dis. 1988 Apr;157(4):842–846. doi: 10.1093/infdis/157.4.842. [DOI] [PubMed] [Google Scholar]
- Barthold S. W., de Souza M. S., Janotka J. L., Smith A. L., Persing D. H. Chronic Lyme borreliosis in the laboratory mouse. Am J Pathol. 1993 Sep;143(3):959–971. [PMC free article] [PubMed] [Google Scholar]
- 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]
- Bergström S., Garon C. F., Barbour A. G., MacDougall J. Extrachromosomal elements of spirochetes. Res Microbiol. 1992 Jul-Aug;143(6):623–628. doi: 10.1016/0923-2508(92)90120-d. [DOI] [PubMed] [Google Scholar]
- Brandt M. E., Riley B. S., Radolf J. D., Norgard M. V. Immunogenic integral membrane proteins of Borrelia burgdorferi are lipoproteins. Infect Immun. 1990 Apr;58(4):983–991. doi: 10.1128/iai.58.4.983-991.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Champion C. I., Blanco D. R., Skare J. T., Haake D. A., Giladi M., Foley D., Miller J. N., Lovett M. A. A 9.0-kilobase-pair circular plasmid of Borrelia burgdorferi encodes an exported protein: evidence for expression only during infection. Infect Immun. 1994 Jul;62(7):2653–2661. doi: 10.1128/iai.62.7.2653-2661.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Dunn J. J., Buchstein S. R., Butler L. L., Fisenne S., Polin D. S., Lade B. N., Luft B. J. Complete nucleotide sequence of a circular plasmid from the Lyme disease spirochete, Borrelia burgdorferi. J Bacteriol. 1994 May;176(9):2706–2717. doi: 10.1128/jb.176.9.2706-2717.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Engstrom S. M., Shoop E., Johnson R. C. Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. J Clin Microbiol. 1995 Feb;33(2):419–427. doi: 10.1128/jcm.33.2.419-427.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fuchs R., Jauris S., Lottspeich F., Preac-Mursic V., Wilske B., Soutschek E. Molecular analysis and expression of a Borrelia burgdorferi gene encoding a 22 kDa protein (pC) in Escherichia coli. Mol Microbiol. 1992 Feb;6(4):503–509. doi: 10.1111/j.1365-2958.1992.tb01495.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Hinnebusch J., Barbour A. G. Linear- and circular-plasmid copy numbers in Borrelia burgdorferi. J Bacteriol. 1992 Aug;174(16):5251–5257. doi: 10.1128/jb.174.16.5251-5257.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hinnebusch J., Tilly K. Linear plasmids and chromosomes in bacteria. Mol Microbiol. 1993 Dec;10(5):917–922. doi: 10.1111/j.1365-2958.1993.tb00963.x. [DOI] [PubMed] [Google Scholar]
- Holt S. C. Anatomy and chemistry of spirochetes. Microbiol Rev. 1978 Mar;42(1):114–160. doi: 10.1128/mr.42.1.114-160.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hyde F. W., Johnson R. C. Characterization of a circular plasmid from Borrelia burgdorferi, etiologic agent of Lyme disease. J Clin Microbiol. 1988 Oct;26(10):2203–2205. doi: 10.1128/jcm.26.10.2203-2205.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lam T. T., Nguyen T. P., Montgomery R. R., Kantor F. S., Fikrig E., Flavell R. A. Outer surface proteins E and F of Borrelia burgdorferi, the agent of Lyme disease. Infect Immun. 1994 Jan;62(1):290–298. doi: 10.1128/iai.62.1.290-298.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marconi R. T., Samuels D. S., Garon C. F. Transcriptional analyses and mapping of the ospC gene in Lyme disease spirochetes. J Bacteriol. 1993 Feb;175(4):926–932. doi: 10.1128/jb.175.4.926-932.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Margolis N., Hogan D., Tilly K., Rosa P. A. Plasmid location of Borrelia purine biosynthesis gene homologs. J Bacteriol. 1994 Nov;176(21):6427–6432. doi: 10.1128/jb.176.21.6427-6432.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller J. F., Mekalanos J. J., Falkow S. Coordinate regulation and sensory transduction in the control of bacterial virulence. Science. 1989 Feb 17;243(4893):916–922. doi: 10.1126/science.2537530. [DOI] [PubMed] [Google Scholar]
- Munderloh U. G., Park Y. J., Dioh J. M., Fallon A. M., Kurtti T. J. Plasmid modifications in a tick-borne pathogen, Borrelia burgdorferi, cocultured with tick cells. Insect Mol Biol. 1993;1(4):195–203. doi: 10.1111/j.1365-2583.1993.tb00092.x. [DOI] [PubMed] [Google Scholar]
- Nguyen T. P., Lam T. T., Barthold S. W., Telford S. R., 3rd, Flavell R. A., Fikrig E. Partial destruction of Borrelia burgdorferi within ticks that engorged on OspE- or OspF-immunized mice. Infect Immun. 1994 May;62(5):2079–2084. doi: 10.1128/iai.62.5.2079-2084.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Norris S. J., Carter C. J., Howell J. K., Barbour A. G. Low-passage-associated proteins of Borrelia burgdorferi B31: characterization and molecular cloning of OspD, a surface-exposed, plasmid-encoded lipoprotein. Infect Immun. 1992 Nov;60(11):4662–4672. doi: 10.1128/iai.60.11.4662-4672.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Olsen G. J., Woese C. R., Overbeek R. The winds of (evolutionary) change: breathing new life into microbiology. J Bacteriol. 1994 Jan;176(1):1–6. doi: 10.1128/jb.176.1.1-6.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Porcella S. F., Popova T. G., Akins D. R., Li M., Radolf J. D., Norgard M. V. Borrelia burgdorferi supercoiled plasmids encode multicopy tandem open reading frames and a lipoprotein gene family. J Bacteriol. 1996 Jun;178(11):3293–3307. doi: 10.1128/jb.178.11.3293-3307.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosa P. A., Schwan T. G. A specific and sensitive assay for the Lyme disease spirochete Borrelia burgdorferi using the polymerase chain reaction. J Infect Dis. 1989 Dec;160(6):1018–1029. doi: 10.1093/infdis/160.6.1018. [DOI] [PubMed] [Google Scholar]
- Rosa P. A., Schwan T., Hogan D. Recombination between genes encoding major outer surface proteins A and B of Borrelia burgdorferi. Mol Microbiol. 1992 Oct;6(20):3031–3040. doi: 10.1111/j.1365-2958.1992.tb01761.x. [DOI] [PubMed] [Google Scholar]
- Sadziene A., Wilske B., Ferdows M. S., Barbour A. G. The cryptic ospC gene of Borrelia burgdorferi B31 is located on a circular plasmid. Infect Immun. 1993 May;61(5):2192–2195. doi: 10.1128/iai.61.5.2192-2195.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Samuels D. S., Garon C. F. Coumermycin A1 inhibits growth and induces relaxation of supercoiled plasmids in Borrelia burgdorferi, the Lyme disease agent. Antimicrob Agents Chemother. 1993 Jan;37(1):46–50. doi: 10.1128/aac.37.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schaible U. E., Gern L., Wallich R., Kramer M. D., Prester M., Simon M. M. Distinct patterns of protective antibodies are generated against Borrelia burgdorferi in mice experimentally inoculated with high and low doses of antigen. Immunol Lett. 1993 May;36(2):219–226. doi: 10.1016/0165-2478(93)90056-8. [DOI] [PubMed] [Google Scholar]
- Schwan T. G., Burgdorfer W., Garon C. F. Changes in infectivity and plasmid profile of the Lyme disease spirochete, Borrelia burgdorferi, as a result of in vitro cultivation. Infect Immun. 1988 Aug;56(8):1831–1836. doi: 10.1128/iai.56.8.1831-1836.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwan T. G., Piesman J., Golde W. T., Dolan M. C., Rosa P. A. Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2909–2913. doi: 10.1073/pnas.92.7.2909. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz J. J., Gazumyan A., Schwartz I. rRNA gene organization in the Lyme disease spirochete, Borrelia burgdorferi. J Bacteriol. 1992 Jun;174(11):3757–3765. doi: 10.1128/jb.174.11.3757-3765.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Simpson W. J., Garon C. F., Schwan T. G. Borrelia burgdorferi contains repeated DNA sequences that are species specific and plasmid associated. Infect Immun. 1990 Apr;58(4):847–853. doi: 10.1128/iai.58.4.847-853.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Stevenson B., Schwan T. G., Rosa P. A. Temperature-related differential expression of antigens in the Lyme disease spirochete, Borrelia burgdorferi. Infect Immun. 1995 Nov;63(11):4535–4539. doi: 10.1128/iai.63.11.4535-4539.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stålhammar-Carlemalm M., Jenny E., Gern L., Aeschlimann A., Meyer J. Plasmid analysis and restriction fragment length polymorphisms of chromosomal DNA allow a distinction between Borrelia burgdorferi strains. Zentralbl Bakteriol. 1990 Oct;274(1):28–39. doi: 10.1016/s0934-8840(11)80972-2. [DOI] [PubMed] [Google Scholar]
- 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]
- Wallich R., Brenner C., Kramer M. D., Simon M. M. Molecular cloning and immunological characterization of a novel linear-plasmid-encoded gene, pG, of Borrelia burgdorferi expressed only in vivo. Infect Immun. 1995 Sep;63(9):3327–3335. doi: 10.1128/iai.63.9.3327-3335.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilske B., Preac-Mursic V., Schierz G., Busch K. V. Immunochemical and immunological analysis of European Borrelia burgdorferi strains. Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):92–102. doi: 10.1016/s0176-6724(86)80108-0. [DOI] [PubMed] [Google Scholar]
- Woese C. R. Bacterial evolution. Microbiol Rev. 1987 Jun;51(2):221–271. doi: 10.1128/mr.51.2.221-271.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Xu Y., Johnson R. C. Analysis and comparison of plasmid profiles of Borrelia burgdorferi sensu lato strains. J Clin Microbiol. 1995 Oct;33(10):2679–2685. doi: 10.1128/jcm.33.10.2679-2685.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zückert W. R., Meyer J. Circular and linear plasmids of Lyme disease spirochetes have extensive homology: characterization of a repeated DNA element. J Bacteriol. 1996 Apr;178(8):2287–2298. doi: 10.1128/jb.178.8.2287-2298.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]