Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 6, Number 2—April 2000
Synopsis

The bdr Gene Families of the Lyme Disease and Relapsing Fever Spirochetes: Potential Influence on Biology, Pathogenesis, and Evolution

David M. Roberts*, Jason A Carlyon†, Michael Theisen, and Richard T. Marconi*Comments to Author 
Author affiliations: *Medical College of Virginia at Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA; †Yale School of Medicine, Yale University, New Haven, Connecticut, USA; ‡Statens Serum Institute, Copenhagen, Denmark

Main Article

Table 1

Borrelia species carrying bdr-related genes or expressing proteins immunoreactive with anti-Bdr antisera

Species Associated disease Arthropod vector Bdr-related information
B.burgdorferi Lyme disease, endemic worldwide I. scapularis, I. ricinus, I. pacificus All bdr-gene family members (18 total) have been identified in isolate B31G (30), bdr-alleles that are organized into 3 subfamilies (D,E,F) (25), the genes are carried on variably sized linear and circular plasmids (30)
B. afzelii Lyme disease, Eurasia I. ricinus, I. persulcatus Single bdr gene has been sequenced (43), several Bdr-related proteins have been detected by immunoblot analysis (this report)
B.garinii Lyme disease, Eurasia I. ricinus, I. persulcatus Bdr proteins detected by immunoblot analyses only (this report)
B. tanukii Not associated with human disease I. tanuki Bdr proteins detected by immunoblot analyses only (this report)
B. turdae Not associated with human disease I. turdus Bdr proteins detected by immunoblot analyses only (this report)
B. bissettii Not associated with human disease I. pacificus, I. scapularis, I. spinipalpis Bdr proteins detected by immunoblot analyses only (this report)
B. andersonii Not associated with human disease I. dentatus bdr genes detected by hybridization and Bdr-related proteins by immunoblot analyses (this report, data not shown)
B. valaisiana Not associated with human disease I. columnae, I. ricinus Bdr proteins detected by immunoblot analyses only (this report)
B. japonica Not associated with human disease I. ovatus Bdr proteins detected by immunoblot analyses only (this report)
B. hermsii Endemic relapsing fever, United States Onithodoros hermsii Numerous bdr genes have been described and are carried on both linear and circular plasmids (25,46); several detected by immunoblot analyses Bdr proteins have been (this report) (44)
B. parkeri Endemic relapsing fever, United States Onithodoros parkeri Two bdr-related genes have been sequenced (25), and others have been detected by hybridization with genes residing on both linear and circular plasmids (46); several Bdr proteins detected by immunoblot analyses (this report)
B. turicatae Endemic relapsing fever, United States O. turicata At least nine bdr-related genes have been described and are present on linear plasmids ranging from 25 to 220 kb in size (24,46); several Bdr proteins have been detected by immunoblotting (this report) (24,44)
B. miyamotoi Relapsing fever? I. persulcatus Bdr proteins detected by immunoblotting only (this report)
B. coriaceae Epizootic bovine abortion, United States O. coriaceus bdr-related genes and proteins detected by hybridization (46) or immunoblotting (this report)
B. anserina Avian spirochetosis, United States Argas persicus bdr-related sequences have been detected by hybridization (46), Bdr- related proteins were not detected in in vitro cultivated bacteria (this report)

Main Article

References
  1. Barbour  AG, Hayes  SF. Biology of Borrelia species. Microbiol Rev. 1986;50:381–400.PubMedGoogle Scholar
  2. Yound  JD. Underreporting of Lyme disease. N Engl J Med. 1998;:338.
  3. Steere  AC, Malawista  SE, Snydman  DR, Shope  RE, Andiman  WA, Ross  MR, Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three Connecticut communities. Arthritis Rheum. 1977;20:7–17. DOIPubMedGoogle Scholar
  4. Burgdorfer  W, Barbour  AG, Hayes  SF, Benach  JL, Grunwaldt  E, Davis  JP. Lyme disease--a tick-borne spirochetosis? Science. 1982;216:1317–9. DOIPubMedGoogle Scholar
  5. Benach  JL, Bosler  EM, Hanrahan  JP, Coleman  JL, Bast  TF, Habicht  GS, Spirochetes isolated from the blood of two patients with Lyme disease. N Engl J Med. 1983;308:740–2.PubMedGoogle Scholar
  6. Baranton  G, Postic  D, Saint Girons  I, Boerlin  P, Piffaretti  J-C, Assous  M, Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461 associated with Lyme borreliosis. Int J Syst Bacteriol. 1992;42:378–83. DOIPubMedGoogle Scholar
  7. Marconi  RT, Garon  CF. Identification of a third genomic group of Borrelia burgdorferi through signature nucleotide analysis and 16S rRNA sequence determination. J Gen Microbiol. 1992;138:533–6.PubMedGoogle Scholar
  8. Marconi  RT, Garon  CF. Phylogenetic analysis of the genus Borrelia: a comparison of North American and European isolates of B. burgdorferi. J Bacteriol. 1992;174:241–4.PubMedGoogle Scholar
  9. Marconi  RT, Liveris  D, Schwartz  I. Identification of novel insertion elements, restriction fragment length polymorphism patterns, and discontinuous 23S rRNA in Lyme Disease spirochetes: phylogenetic analyses of rRNA genes and their intergenic spacers in Borrelia japonica sp. nov. and genomic group 21038 (Borrelia andersonii sp. nov.) isolates. J Clin Microbiol. 1995;33:2427–34.PubMedGoogle Scholar
  10. Fukunaga  M, Hamase  A, Okada  K, Inoue  H, Tsuruta  Y, Miyamoto  K, Characterization of spirochetes isolated from ticks (Ixodes tanukin, I. turdus and Ixodes columnae) and comparision of the sequences with those of Borrelia burgdorferi sensu lato strains. Appl Environ Microbiol. 1996;62:2338–44.PubMedGoogle Scholar
  11. Fukunaga  M, Hamase  A, Okada  K, Nakao  M. sp. nov. and Borrelia turdae sp. nov. found from Ixodid ticks in Japan: rapid species identification by 16S rRNA gene--targeted PCR analysis. Microbiol Immunol. 1996;40:877–81.Borrelia tanukiPubMedGoogle Scholar
  12. Fukunaga  M, Takahashi  Y, Tsuruta  Y, Matsushita  O, Ralph  D, McClelland  M, Genetic and phenotypic analysis of Borrelia miyamotoi sp. nov., isolates from the Ixodid tick Ixodes persulcatus, the vector for Lyme disease in Japan. Int J Syst Bacteriol. 1995;45:804–10. DOIPubMedGoogle Scholar
  13. Wang  G, van Dam  AP, Le Flecha  A, Postic  D, Peter  O, Baranton  G, Genetic and phenotypic analysis of Borrelia valaisiana sp. nov. (Borrelia genomic groups VS116 and M19). Int J Syst Bacteriol. 1997;47:926–32. DOIPubMedGoogle Scholar
  14. Postic  D, Belfazia  J, Isogai  E, Saint Girons  I, Grimont  PAD, Baranton  G. A new genomic species in Borrelia burgdorferi sensu lato isolated from Japanese ticks. Res Microbiol. 1993;144:467–73. DOIPubMedGoogle Scholar
  15. Postic  D, Edlinger  C, Richaud  C, Grimont  F, Dufresne  Y, Perolat  P, Two genomic species in Borrelia burgdorferi. Res Microbiol. 1990;141:465–75. DOIPubMedGoogle Scholar
  16. Barbour  AG. Antigenic variation of a relapsing fever Borrelia species. Annu Rev Microbiol. 1990;44:155–71. DOIPubMedGoogle Scholar
  17. Barbour  AG, Byrman  N, Carter  CJ, Kitten  T, Berstrom  S. Variable antigen genes of the replasing fever agent Borrelia hermsii are activated by promoter addition. Mol Microbiol. 1991;5:489–93. DOIPubMedGoogle Scholar
  18. Stoenner  HG, Dodd  T, Larsen  C. Antigenic variation of B. hermsii. J Exp Med. 1982;156:1297–311. DOIPubMedGoogle Scholar
  19. Plasterk  RHA, Simon  MI, Barbour  AG. Transposition of structural genes to an expression sequence on a linear plasmid causes antigenic variation in the bacterium B. hermsii. Nature. 1985;318:257–63. DOIPubMedGoogle Scholar
  20. Zhang  J-R, Hardham  JM, Barbour  AG, Norris  AG. Antigenic variation in Lyme disease Borreliae by promiscuous recombination of vmp like sequence cassettes. Cell. 1997;89:275–85. DOIPubMedGoogle Scholar
  21. 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;31:2577–83.PubMedGoogle Scholar
  22. Schwan  TG, Piesman  J, Golde  WT, Dolan  MC, Rosa  PA. Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc Natl Acad Sci U S A. 1995;92:2909–13. DOIPubMedGoogle Scholar
  23. Schwan  TG, Hinnebusch  BJ. Bloodstream- versus tick- associated variants of a Relapsing fever bacterium. Science. 1998;280:1938–40. DOIPubMedGoogle Scholar
  24. Carlyon  JA, Roberts  DM, Theisen  M, Marconi  RT. Molecular analyses of the B. turicatae bdr genes: a polymorphic, linear plasmid carried, paralogous gene family. In press 1999.
  25. Carlyon  JA, Roberts  DM, Marconi  RT. Evolutionary and molecular analyses of the Borrelia rep super gene family: delineation of six distinct sub-families and demonstration of the genus wide conservation of putative functional domains, structural properties and repeat motifs. Microb Pathog. 2000. In press.PubMedGoogle Scholar
  26. Ferdows  MS, Barbour  AG. Megabase-sized linear DNA in the bacterium Borrelia burgdorferi, the Lyme disease agent. Proc Natl Acad Sci U S A. 1989;86:5969–73. DOIPubMedGoogle Scholar
  27. Barbour  AG, Garon  CF. Linear plasmids of the bacterium Borrelia burgdorferi have covalently closed ends. Science. 1987;237:409–11. DOIPubMedGoogle Scholar
  28. Barbour  AG. Plasmid analysis of Borrelia burgdorferi, the Lyme disease agent. J Clin Microbiol. 1988;26:475–8.PubMedGoogle Scholar
  29. Hinnebusch  J, Barbour  AG. Linear plasmids of Borrelia burgdorferi have a telomeric structure and sequence similar to those of a eukaryotic virus. J Bacteriol. 1991;173:7233–9.PubMedGoogle Scholar
  30. Fraser  C, Casjens  S, Huang  WM, Sutton  GG, Clayton  R, Lathigra  R, Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature. 1997;390:580–6. DOIPubMedGoogle Scholar
  31. Barbour  AG. Linear DNA of Borrelia species and antigenic variation. Trends Microbiol. 1993;:1.PubMedGoogle Scholar
  32. Hinnebusch  J, Tilly  K. Linear plasmids and chromosomes in bacteria. Mol Microbiol. 1993;10:917–22. DOIPubMedGoogle Scholar
  33. Hinnebusch  J, Barbour  AG. Linear- and circular-plasmid copy numbers in Borrelia burgdorferi. J Bacteriol. 1992;174:5251–7.PubMedGoogle Scholar
  34. Champion  CI, Blanco  DR, Skare  JT, Haake  DA, Giladi  M, Foley  D, A 9.0 kilobase-pair circular plasmid of Borrelia burgdorferi encodes an exported protein: evidence for expression only during infection. Infect Immun. 1994;62:2653–61.PubMedGoogle Scholar
  35. Akins  D, Porcella  SF, Popova  TG, Shevchenko  D, Baker  SI, Li  M, Evidence for in vivo but not in vitro expression of a Borrelia burgdorferi outer surface protein F (OspF) homologue. Mol Microbiol. 1995;18:507–20. DOIPubMedGoogle Scholar
  36. Suk  K, Das  S, Sun  W, Jwang  B, Barthold  SW, Flavell  RA, Borrelia burgdorferi genes selectively expressed in the infected host. Proc Natl Acad Sci U S A. 1995;92:4269–73. DOIPubMedGoogle Scholar
  37. Skare  JT, Foley  DM, Hernandez  SR, Moore  DC, Blanco  DR, Miller  JN, Cloning and molecular characterization of plasmid-encoded antigens of Borrelia burgdorferi. Infect Immun. 1999;67:4407–17.PubMedGoogle Scholar
  38. Marconi  RT, Sung  SY, Hughes  CN, Carlyon  JA. Molecular and evolutionary analyses of a variable series of genes in Borrelia burgdorferi that are related to ospE and ospF, constitute a gene family, and share a common upstream homology box. J Bacteriol. 1996;178:5615–26.PubMedGoogle Scholar
  39. Sung  S-Y, LaVoie  C, Carlyon  JA, Marconi  RT. Evolutionary instability of ospE related members of the UHB gene family in Borrelia burgdorferi sensu lato complex isolates. Infect Immun. 1998;66:4656–68.PubMedGoogle Scholar
  40. Zhang  JR, Norris  SJ. Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion. Infect Immun. 1998;66:3698–704.PubMedGoogle Scholar
  41. Zuckert  WR, Meyer  J. Circular and linear plasmids of Lyme Disease spirochetes have extensive homology: characterization of a repeated DNA element. J Bacteriol. 1996;178:2287–98.PubMedGoogle Scholar
  42. Porcella  SF, Popova  TG, Akins  DR, Li  M, Radolf  JR, Norgard  MV. Borrelia burgdorferi supercoiled plasmids encode multicopy open reading frames and a lipoprotein gene family. J Bacteriol. 1996;178:3293–307.PubMedGoogle Scholar
  43. Theisen  M. Molecular cloning and characterization of nlpH, encoding a novel surface exposed, polymorphic, plasmid-encoded 33kD lipoprotein of Borrelia afzelii. J Bacteriol. 1996;178:6435–42.PubMedGoogle Scholar
  44. Zuckert  WR, Meyer  J, Barbour  AG. Comparative analysis and immunological characterization of the Borrelia Bdr protein family. Infect Immun. 1999;67:3257–66.PubMedGoogle Scholar
  45. Yang  X, Popova  TG, Hagman  KE, Wikel  SK, Schoeler  GB, Caimano  MJ, Identification, characterization, and expression of three new members of the Borrelia burgdorferi Mlp (2.9) lipoprotein gene family. Infect Immun. 1999;67:6008–18.PubMedGoogle Scholar
  46. Carlyon  JA, Marconi  RT. Cloning and molecular characterization of a multi-copy, linear plasmid-carried, repeat motif-containing gene from Borrelia turicatae, a causative agent of relapsing fever. J Bacteriol. 1998;180:4974–81.PubMedGoogle Scholar
  47. Reeves  PR, Hobbs  M, Valvano  MA, Kido  N, Klena  J, Maskell  D, Bacterial polysaccharide synthesis and gene nomenclature. Trends Microbiol. 1996;4:498–503. DOIGoogle Scholar
  48. Demerec  M. A proposal for a uniform nomenclature in bacterial genetics. Genetics. 1966;54:61–76.PubMedGoogle Scholar
  49. Pinna  LA. Casein kinase 2: an "eminence grise" in cellular regulation. Biochim Biophys Acta. 1990;1054:267–84. DOIPubMedGoogle Scholar
  50. Shi  L, Potts  M, Kennelly  PJ. The serine, threonine and/or tyrosine protein kinases and protein phosphatases of procaryotic organisms: a family portrait. FEMS Microbiol Rev. 1998;22:229–53. DOIPubMedGoogle Scholar
  51. Xu  Y, Kodner  C, Coleman  L, Johnson  RC. Correlation of plasmids with infectivity of Borrelia burgdorferi sensu stricto type strain B31. Infect Immun. 1996;64:3870–6.PubMedGoogle Scholar
  52. Xu  Y, Johnson  RC. Analysis and comparision of plasmid profiles of Borrelia burgdorferi sensu lato strains. J Clin Microbiol. 1995;33:2679–85.PubMedGoogle Scholar
  53. 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;274:28–39.PubMedGoogle Scholar
  54. Simpson  WJ, Garon  CF, Schwan  TG. Analysis of supercoiled circular plasmids in infectious and non-infectious Borrelia burgdorferi. Microb Pathog. 1990;8:109–18. DOIPubMedGoogle Scholar
  55. Schwan  TG, Schrumpf  ME, Karstens  RH, Clover  JR, Wong  J, Daugherty  M, Distribution and molecular analysis of Lyme disease spirochetes, Borrelia burgdorferi, isolated from ticks throughout California. J Clin Microbiol. 1993;31:3096–108.PubMedGoogle Scholar
  56. Marconi  RT, Casjens  S, Munderloh  UG, Samuels  DS. Analysis of linear plasmid dimers in Borrelia burgdorferi sensu lato isolates: implications concerning the potential mechanism of linear plasmid replication. J Bacteriol. 1996;178:3357–61.PubMedGoogle Scholar
  57. 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;176:4572–82.PubMedGoogle Scholar
  58. Ferdows  MS, Serwer  P, Griess  GA, Norris  SJ, Barbour  AG. Conversion of a linear to a circular plasmid in the relapsing fever agent Borrelia hermsii. J Bacteriol. 1996;178:793–800.PubMedGoogle Scholar
  59. Carlyon  JA, LaVoie  C, Sung  SY, Marconi  RT. Analysis of the organization of multi-copy linear and circular plasmid carried open reading frames in Borrelia burgdorferi sensu lato isolates. Infect Immun. 1998;66:1149–58.PubMedGoogle Scholar

Main Article

Page created: December 16, 2010
Page updated: December 16, 2010
Page reviewed: December 16, 2010
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external