Logo of jcmPermissionsJournals.ASM.orgJournalJCM ArticleJournal InfoAuthorsReviewers
J Clin Microbiol. Jul 1995; 33(7): 1860–1866.
PMCID: PMC228286

Molecular analysis of genes encoding outer surface protein C (OspC) of Borrelia burgdorferi sensu lato: relationship to ospA genotype and evidence of lateral gene exchange of ospC.

Abstract

It has been shown by analysis with monoclonal and polyclonal antibodies that outer surface protein C (OspC) of Borrelia burgdorferi sensu lato is highly heterogeneous. To determine if the heterogeneity has a genetic basis, the genes of 18 different B. burgdorferi sensu lato strains have been amplified by PCR, cloned, and sequenced. The ospC genes could be amplified from all strains tested, even from two strains which did not express OspC in detectable amounts. Among the 18 strains, 16 significantly different types of ospC sequences have been found. The sequence identities of the deduced amino acid sequences of different ospC genotypes range between 62 and 80% (determined without the leader peptide). The sequences range between 62 and 80% (determined without the leader peptide). The sequences correspond to one of the 13 OspC types distinguishable by analysis with monoclonal antibodies (B. Wilske, S. Jauris-Heipke, R. Lobentanzer, I. Pradel, V. Preac-Mursic, D. Roessler, E. Soutschek, and R. C. Johnson, J. Clin. Microbiol. 33:103-109, 1995) or represent additional types. Two completely new types were found, and OspC type 8 (which was found in Borrelia afzelii and Borrelia garinii) could be divided into two groups with different sequences but the same antibody pattern. Thus, strains belonging to different species or OspA serotypes were always significantly different in their ospC sequences. This was also confirmed by ospA sequence analysis. Interestingly, some strains of the same OspA serotype or genotype were very heterogeneous with respect to OspC, while others had nearly identical OspC proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Full Text

The Full Text of this article is available as a PDF (247K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aguero-Rosenfeld ME, Nowakowski J, McKenna DF, Carbonaro CA, Wormser GP. Serodiagnosis in early Lyme disease. J Clin Microbiol. 1993 Dec;31(12):3090–3095. [PMC free article] [PubMed]
  • Assous MV, Postic D, Paul G, Névot P, Baranton G. Individualisation of two new genomic groups among American Borrelia burgdorferi sensu lato strains. FEMS Microbiol Lett. 1994 Aug 1;121(1):93–98. [PubMed]
  • Baranton G, Postic D, Saint Girons I, Boerlin P, Piffaretti JC, Assous M, Grimont PA. Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461 associated with Lyme borreliosis. Int J Syst Bacteriol. 1992 Jul;42(3):378–383. [PubMed]
  • Temin HM. Mechanisms of cell killing/cytopathic effects by nonhuman retroviruses. Rev Infect Dis. 1988 Mar-Apr;10(2):399–405. [PubMed]
  • Barbour AG, Heiland RA, Howe TR. Heterogeneity of major proteins in Lyme disease borreliae: a molecular analysis of North American and European isolates. J Infect Dis. 1985 Sep;152(3):478–484. [PubMed]
  • Barbour AG, Schrumpf ME. Polymorphisms of major surface proteins of Borrelia burgdorferi. Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):83–91. [PubMed]
  • Burgdorfer W, Barbour AG, Hayes SF, Benach JL, Grunwaldt E, Davis JP. Lyme disease-a tick-borne spirochetosis? Science. 1982 Jun 18;216(4552):1317–1319. [PubMed]
  • Cadavid D, Thomas DD, Crawley R, Barbour AG. Variability of a bacterial surface protein and disease expression in a possible mouse model of systemic Lyme borreliosis. J Exp Med. 1994 Feb 1;179(2):631–642. [PMC free article] [PubMed]
  • Canica MM, Nato F, du Merle L, Mazie JC, Baranton G, Postic D. Monoclonal antibodies for identification of Borrelia afzelii sp. nov. associated with late cutaneous manifestations of Lyme borreliosis. Scand J Infect Dis. 1993;25(4):441–448. [PubMed]
  • Carter CJ, Bergström S, Norris SJ, Barbour AG. A family of surface-exposed proteins of 20 kilodaltons in the genus Borrelia. Infect Immun. 1994 Jul;62(7):2792–2799. [PMC free article] [PubMed]
  • Comstock LE, Fikrig E, Shoberg RJ, Flavell RA, Thomas DD. A monoclonal antibody to OspA inhibits association of Borrelia burgdorferi with human endothelial cells. Infect Immun. 1993 Feb;61(2):423–431. [PMC free article] [PubMed]
  • Devereux J, Haeberli P, Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. [PMC free article] [PubMed]
  • Dressler F, Whalen JA, Reinhardt BN, Steere AC. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis. 1993 Feb;167(2):392–400. [PubMed]
  • Dykhuizen DE, Polin DS, Dunn JJ, Wilske B, Preac-Mursic V, Dattwyler RJ, Luft BJ. Borrelia burgdorferi is clonal: implications for taxonomy and vaccine development. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10163–10167. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Fung BP, McHugh GL, Leong JM, Steere AC. Humoral immune response to outer surface protein C of Borrelia burgdorferi in Lyme disease: role of the immunoglobulin M response in the serodiagnosis of early infection. Infect Immun. 1994 Aug;62(8):3213–3221. [PMC free article] [PubMed]
  • Howe TR, Mayer LW, Barbour AG. A single recombinant plasmid expressing two major outer surface proteins of the Lyme disease spirochete. Science. 1985 Feb 8;227(4687):645–646. [PubMed]
  • Hughes CA, Engstrom SM, Coleman LA, Kodner CB, Johnson RC. Protective immunity is induced by a Borrelia burgdorferi mutant that lacks OspA and OspB. Infect Immun. 1993 Dec;61(12):5115–5122. [PMC free article] [PubMed]
  • Jauris-Heipke S, Fuchs R, Motz M, Preac-Mursic V, Schwab E, Soutschek E, Will G, Wilske B. Genetic heterogenity of the genes coding for the outer surface protein C (OspC) and the flagellin of Borrelia burgdorferi. Med Microbiol Immunol. 1993 Mar;182(1):37–50. [PubMed]
  • Jonsson M, Noppa L, Barbour AG, Bergström S. Heterogeneity of outer membrane proteins in Borrelia burgdorferi: comparison of osp operons of three isolates of different geographic origins. Infect Immun. 1992 May;60(5):1845–1853. [PMC free article] [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Langenberg W, Rauws EA, Widjojokusumo A, Tytgat GN, Zanen HC. Identification of Campylobacter pyloridis isolates by restriction endonuclease DNA analysis. J Clin Microbiol. 1986 Sep;24(3):414–417. [PMC free article] [PubMed]
  • Luft BJ, Steinman CR, Neimark HC, Muralidhar B, Rush T, Finkel MF, Kunkel M, Dattwyler RJ. Invasion of the central nervous system by Borrelia burgdorferi in acute disseminated infection. JAMA. 1992 Mar 11;267(10):1364–1367. [PubMed]
  • Marconi RT, Samuels DS, Garon CF. Transcriptional analyses and mapping of the ospC gene in Lyme disease spirochetes. J Bacteriol. 1993 Feb;175(4):926–932. [PMC free article] [PubMed]
  • Marconi RT, Samuels DS, Landry RK, Garon CF. Analysis of the distribution and molecular heterogeneity of the ospD gene among the Lyme disease spirochetes: evidence for lateral gene exchange. J Bacteriol. 1994 Aug;176(15):4572–4582. [PMC free article] [PubMed]
  • Marconi RT, Samuels DS, Schwan TG, Garon CF. Identification of a protein in several Borrelia species which is related to OspC of the Lyme disease spirochetes. J Clin Microbiol. 1993 Oct;31(10):2577–2583. [PMC free article] [PubMed]
  • Margolis N, Hogan D, Cieplak W, Jr, Schwan TG, Rosa PA. Homology between Borrelia burgdorferi OspC and members of the family of Borrelia hermsii variable major proteins. Gene. 1994 May 27;143(1):105–110. [PubMed]
  • Margolis N, Hogan D, Tilly K, Rosa PA. Plasmid location of Borrelia purine biosynthesis gene homologs. J Bacteriol. 1994 Nov;176(21):6427–6432. [PMC free article] [PubMed]
  • Norris SJ, Carter CJ, Howell JK, Barbour AG. 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. [PMC free article] [PubMed]
  • Padula SJ, Dias F, Sampieri A, Craven RB, Ryan RW. Use of recombinant OspC from Borrelia burgdorferi for serodiagnosis of early Lyme disease. J Clin Microbiol. 1994 Jul;32(7):1733–1738. [PMC free article] [PubMed]
  • Padula SJ, Sampieri A, Dias F, Szczepanski A, Ryan RW. Molecular characterization and expression of p23 (OspC) from a North American strain of Borrelia burgdorferi. Infect Immun. 1993 Dec;61(12):5097–5105. [PMC free article] [PubMed]
  • Preac-Mursic V, Wilske B, Patsouris E, Jauris S, Will G, Soutschek E, Rainhardt S, Lehnert G, Klockmann U, Mehraein P. Active immunization with pC protein of Borrelia burgdorferi protects gerbils against B. burgdorferi infection. Infection. 1992 Nov-Dec;20(6):342–349. [PubMed]
  • Preac-Mursic V, Wilske B, Schierz G. European Borrelia burgdorferi isolated from humans and ticks culture conditions and antibiotic susceptibility. Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):112–118. [PubMed]
  • Probert WS, LeFebvre RB. Protection of C3H/HeN mice from challenge with Borrelia burgdorferi through active immunization with OspA, OspB, or OspC, but not with OspD or the 83-kilodalton antigen. Infect Immun. 1994 May;62(5):1920–1926. [PMC free article] [PubMed]
  • Rosa PA, 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. [PubMed]
  • Sădziene A, Rosa PA, Thompson PA, Hogan DM, Barbour AG. Antibody-resistant mutants of Borrelia burgdorferi: in vitro selection and characterization. J Exp Med. 1992 Sep 1;176(3):799–809. [PMC free article] [PubMed]
  • Sadziene A, Thompson PA, Barbour AG. In vitro inhibition of Borrelia burgdorferi growth by antibodies. J Infect Dis. 1993 Jan;167(1):165–172. [PubMed]
  • Sadziene A, Wilske B, Ferdows MS, Barbour AG. The cryptic ospC gene of Borrelia burgdorferi B31 is located on a circular plasmid. Infect Immun. 1993 May;61(5):2192–2195. [PMC free article] [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Stevenson B, Barthold SW. Expression and sequence of outer surface protein C among North American isolates of Borrelia burgdorferi. FEMS Microbiol Lett. 1994 Dec 15;124(3):367–372. [PubMed]
  • Stevenson B, Bockenstedt LK, Barthold SW. Expression and gene sequence of outer surface protein C of Borrelia burgdorferi reisolated from chronically infected mice. Infect Immun. 1994 Aug;62(8):3568–3571. [PMC free article] [PubMed]
  • Theisen M, Frederiksen B, Lebech AM, Vuust J, Hansen K. Polymorphism in ospC gene of Borrelia burgdorferi and immunoreactivity of OspC protein: implications for taxonomy and for use of OspC protein as a diagnostic antigen. J Clin Microbiol. 1993 Oct;31(10):2570–2576. [PMC free article] [PubMed]
  • van Dam AP, Kuiper H, Vos K, Widjojokusumo A, de Jongh BM, Spanjaard L, Ramselaar AC, Kramer MD, Dankert J. Different genospecies of Borrelia burgdorferi are associated with distinct clinical manifestations of Lyme borreliosis. Clin Infect Dis. 1993 Oct;17(4):708–717. [PubMed]
  • Vieira J, Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. [PubMed]
  • Wilske B, Fingerle V, Herzer P, Hofmann A, Lehnert G, Peters H, Pfister HW, Preac-Mursic V, Soutschek E, Weber K. Recombinant immunoblot in the serodiagnosis of Lyme borreliosis. Comparison with indirect immunofluorescence and enzyme-linked immunosorbent assay. Med Microbiol Immunol. 1993 Nov;182(5):255–270. [PubMed]
  • Wilske B, Fingerle V, Preac-Mursic V, Jauris-Heipke S, Hofmann A, Loy H, Pfister HW, Rössler D, Soutschek E. Immunoblot using recombinant antigens derived from different genospecies of Borrelia burgdorferi sensu lato. Med Microbiol Immunol. 1994 Feb;183(1):43–59. [PubMed]
  • Wilske B, Jauris-Heipke S, Lobentanzer R, Pradel I, Preac-Mursic V, Rössler D, Soutschek E, Johnson RC. Phenotypic analysis of outer surface protein C (OspC) of Borrelia burgdorferi sensu lato by monoclonal antibodies: relationship to genospecies and OspA serotype. J Clin Microbiol. 1995 Jan;33(1):103–109. [PMC free article] [PubMed]
  • Wilske B, Preac-Mursic V, Göbel UB, Graf B, Jauris S, Soutschek E, Schwab E, Zumstein G. An OspA serotyping system for Borrelia burgdorferi based on reactivity with monoclonal antibodies and OspA sequence analysis. J Clin Microbiol. 1993 Feb;31(2):340–350. [PMC free article] [PubMed]
  • Wilske B, Preac-Mursic V, Jauris S, Hofmann A, Pradel I, Soutschek E, Schwab E, Will G, Wanner G. Immunological and molecular polymorphisms of OspC, an immunodominant major outer surface protein of Borrelia burgdorferi. Infect Immun. 1993 May;61(5):2182–2191. [PMC free article] [PubMed]
  • Wilske B, Preac-Mursic V, Schierz G, Kühbeck R, Barbour AG, Kramer M. Antigenic variability of Borrelia burgdorferi. Ann N Y Acad Sci. 1988;539:126–143. [PubMed]
  • Wilske B, Preac-Mursic V, Schierz G, Busch KV. Immunochemical and immunological analysis of European Borrelia burgdorferi strains. Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):92–102. [PubMed]
  • Wilske B, Schierz G, Preac-Mursic V, von Busch K, Kühbeck R, Pfister HW, Einhäupl K. Intrathecal production of specific antibodies against Borrelia burgdorferi in patients with lymphocytic meningoradiculitis (Bannwarth's syndrome). J Infect Dis. 1986 Feb;153(2):304–314. [PubMed]
  • Yanisch-Perron C, Vieira J, Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. [PubMed]
  • Zumstein G, Fuchs R, Hofmann A, Preac-Mursic V, Soutschek E, Wilske B. Genetic polymorphism of the gene encoding the outer surface protein A (OspA) of Borrelia burgdorferi. Med Microbiol Immunol. 1992;181(2):57–70. [PubMed]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...