Wiener klinische Wochenschrift

, Volume 118, Issue 21–22, pp 643–652 | Cite as

Evolving models of Lyme disease spirochete gene regulation

  • Brian Stevenson
  • Kate von Lackum
  • Sean P. Riley
  • Anne E. Cooley
  • Michael E. Woodman
  • Tomasz Bykowski
Review Article

Summary

The spirochete Borrelia burgdorferi, the causative agent of Lyme disease (Lyme borreliosis), is well-adapted to maintain a natural cycle of alternately infecting vertebrates and blood-sucking ticks. During this cycle, B. burgdorferi interacts with a broad spectrum of vertebrate and arthropod tissues, acquires nutrients in diverse environments and evades killing by vertebrate and tick immune systems. The bacterium also senses when situations occur that necessitate transmission between hosts, such as when an infected tick is taking a blood meal from a potential host. To accurately accomplish the requirements necessary for survival in nature, B. burgdorferi must be keenly aware of its surroundings and respond accordingly. In this review, we trace studies performed to elucidate regulatory mechanisms employed by B. burgdorferi to control gene expression, and the development of models or "paradigms" to explain experimental results. Through comparisons of five borrelial gene families, it is readily apparent that each is controlled through a distinct mechanism. Furthermore, those results indicate that current models of interpreting in vitro data cannot accurately predict all aspects of B. burgdorferi environmental sensing and gene regulation in vivo.

Keywords

Borrelia burgdorferi Gene regulation Bacteria Model 

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References

  1. Indest KJ, Ramamoorthy R, Philipp MT (2001) Transcriptional regulation in spirochetes of medical importance. In: Saier MH, García-Lara J (eds) The spirochetes: molecular and cellular biology. Horizon Press, Oxford, pp 159–170Google Scholar
  2. Pal U, Fikrig E (2003) Adaptation of Borrelia burgdorferi in the vector and vertebrate host. Microbes Infect 5: 659–666PubMedCrossRefGoogle Scholar
  3. Seshu J, Skare JT (2001) The many faces of Borrelia burgdorferi. In: Saier MH, García-Lara J (eds) The spirochetes: molecular and cellular biology. Horizon Press, Oxford, pp 147–158Google Scholar
  4. Kuhn TS (1970) The structure of scientific revolutions. University of Chicago Press, ChicagoGoogle Scholar
  5. Schwan TG, Piesman J, Golde WT, Dolan MC, Rosa PA (1995) Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc Natl Acad Sci USA 92: 2909–2913PubMedCrossRefGoogle Scholar
  6. Gilmore RD Jr, Piesman J (2000) Inhibition of Borrelia burgdorferi migration from the midgut to the salivary glands following feeding by ticks on OspC-immunized mice. Infect Immun 68: 411–414PubMedCrossRefGoogle Scholar
  7. Grimm D, Tilly K, Byram R, Stewart PE, Krum JG, Bueschel DM, et al (2004) Outer-surface protein C of the Lyme disease spirochete: a protein induced in ticks for infection of mammals. Proc Natl Acad Sci USA 101: 3142–3147PubMedCrossRefGoogle Scholar
  8. Pal U, Yang X, Chen M, Bockenstedt LK, Anderson JF, Flavell RA, et al (2004) OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands. J Clin Invest 113: 220–230PubMedCrossRefGoogle Scholar
  9. Ramamoorthi N, Narasimhan S, Pal U, Bao F, Yang XF, Fish D, et al (2005) The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature 436: 573–577PubMedCrossRefGoogle Scholar
  10. Rosa PA (2005) Lyme disease agent borrows a practical coat. Nat Med 11: 831–832PubMedCrossRefGoogle Scholar
  11. Schwan TG, Piesman J (2000) Temporal changes in outer surface proteins A and C of the Lyme disease-associated spirochete, Borrelia burgdorferi, during the chain of infection in ticks and mice. J Clin Microbiol 38: 382–388PubMedGoogle Scholar
  12. Miller JC, von Lackum K, Babb K, McAlister JD, Stevenson B (2003) Temporal analysis of Borrelia burgdorferi Erp protein expression throughout the mammal-tick infectious cycle. Infect Immun 71: 6943–6952PubMedCrossRefGoogle Scholar
  13. Ohnishi J, Piesman J, de Silva AM (2001) Antigenic and genetic heterogeneity of Borrelia burgdorferi populations transmitted by ticks. Proc Natl Acad Sci USA 98: 670–675PubMedCrossRefGoogle Scholar
  14. Crippa M, Rais O, Gern L (2002) Investigations on the mode and dynamics of transmission and infectivity of Borrelia burgdorferi sensu stricto and Borrelia afzelii in Ixodes ricinus ticks. Vector Borne Zoon Dis 2: 3–9CrossRefGoogle Scholar
  15. des Vignes F, Piesman J, Heffernan R, Schultze TL, Stafford KC, Fish D (2001) Effect of tick removal on transmission of Borrelia burgdorferi and Ehrlichia phagocytophila by Ixodes scapularis nymphs. J Inf Dis 183: 773–778CrossRefGoogle Scholar
  16. Piesman J, Maupin GO, Campos EG, Happ CM (1991) Duration of adult female Ixodes dammini attachment and transmission of Borrelia burgdorferi, with description of a needle aspiration isolation method. J Infect Dis 163: 895–897PubMedGoogle Scholar
  17. Sood SK, Salzman MB, Johnson BJB, Happ CM, Feig K, Carmody L, et al (1997) Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic. J Infect Dis 175: 996–999PubMedGoogle Scholar
  18. Konkel ME, Tilly K (2000) Temperature-regulated expression of bacterial virulence genes. Microbes Infect 2: 157–166PubMedCrossRefGoogle Scholar
  19. Stevenson B, Schwan TG, Rosa PA (1995) Temperaturerelated differential expression of antigens in the Lyme disease spirochete, Borrelia burgdorferi. Infect Immun 63: 4535–4539PubMedGoogle Scholar
  20. Barthold SW, Fikrig E, Bockenstedt LK, Persing DH (1995) Circumvention of outer surface protein A immunity by host-adapted Borrelia burgdorferi. Infect Immun 63: 2255–2261PubMedGoogle Scholar
  21. Burkot TR, Piesman J, Wirtz RA (1994) Quantitation of the Borrelia burgdorferi outer surface protein A in Ixodes scapularis: fluctuations during the tick life cycle, doubling times and loss while feeding. J Infect Dis 170: 883–889PubMedGoogle Scholar
  22. Cassatt DR, Patel NK, Ulbrandt ND, Hanson MS (1998) DbpA, but not OspA, is expressed by Borrelia burgdorferi during spirochetemia and is a target for protective antibodies. Infect Immun 66: 5379–5387PubMedGoogle Scholar
  23. Crother TR, Champion CI, Wu X-Y, Blanco DR, Miller JN, Lovett MA (2003) Antigenic composition of Borrelia burgdorferi during infection of SCID mice. Infect Immun 71: 3419–3428PubMedCrossRefGoogle Scholar
  24. Fikrig E, Telford SR, Barthold SW, Kantor FS, Spielman A, Flavell RA (1992) Elimination of Borrelia burgdorferi from vector ticks feeding on OspA-immunized mice. Proc Natl Acad Sci USA 89: 5418–5421PubMedCrossRefGoogle Scholar
  25. Fingerle V, Hauser U, Liegl G, Petko B, Preac-Mursic V, Wilske B (1995) Expression of outer surface proteins A and C of Borrelia burgdorferi in Ixodes ricinus. J Clin Microbiol 33: 1867–1869PubMedGoogle Scholar
  26. Hodzic E, Feng S, Freet KJ, Borjesson DL, Barthold SW (2002) Borrelia burgdorferi population kinetics and selected gene expression at the host-vector interface. Infect Immun 70: 3382–3388PubMedCrossRefGoogle Scholar
  27. Leuba-Garcia S, Martinez R, Gern L (1998) Expression of outer surface proteins A and C of Borrelia afzelii in Ixodes ricinus ticks and in the skin of mice. Zentralbl Bakteriol 287: 475–484PubMedGoogle Scholar
  28. Margolis N, Rosa PA (1993) Regulation of expression of major outer surface proteins in Borrelia burgdorferi. Infect Immun 61: 2207–2210PubMedGoogle Scholar
  29. Montgomery RR, Malawista SE, Feen KJM, Bockenstedt LK (1996) Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo: exploration of the paradox of the early immune response to outer surface proteins A and C in Lyme disease. J Exp Med 183: 261–269PubMedCrossRefGoogle Scholar
  30. Philipp MT (1998) Studies on OspA: a source of new paradigms in Lyme disease research. Trends Microbiol 6: 44–47PubMedCrossRefGoogle Scholar
  31. Piesman J, Zeidner NS, Schneider BS (2003) Dynamic changes in Borrelia burgdorferi populations in Ixodes scapularis (Acari: Ixodidae) during transmission: studies at the mRNA level. Vector Borne Zoonotic Dis 3: 125–132PubMedCrossRefGoogle Scholar
  32. Pal U, Li X, Wang T, Montgomery RR, Ramamoorthi N, deSilva AM, et al (2004) TROSPA, an Ixodes scapularis receptor for Borrelia burgdorferi. Cell 119: 457–468PubMedCrossRefGoogle Scholar
  33. Yang XF, Pal U, Alani SM, Fikrig E, Norgard MV (2004) Essential role for OspA/B in the life cycle of the Lyme disease spirochete. J Exp Med 199: 641–648PubMedCrossRefGoogle Scholar
  34. Akins DR, Bourell KW, Caimano MJ, Norgard MV, Radolf JD (1998) A new animal model for studying Lyme disease spirochetes in a mammalian host-adapted state. J Clin Invest 101: 2240–2250PubMedGoogle Scholar
  35. Dobrikova EY, Bugrysheva J, Cabello FC (2001) Two independent transcriptional units control the complex and simultaneous expression of the bmp paralogous chromosomal gene family in Borrelia burgdorferi. Mol Microbiol 39: 370–378PubMedCrossRefGoogle Scholar
  36. Hodzic E, Feng S, Freet KJ, Barthold SW (2003) Borrelia burgdorferi population dynamics and prototype gene expression during infection of immunocompetent and immunodeficient mice. Infect Immun 71: 5042–5055PubMedCrossRefGoogle Scholar
  37. Narasimhan S, Caimano MJ, Liang FT, Santiago F, Laskowski M, Philipp MT, et al (2003) Borrelia burgdorferi transcriptome in the central nervous system of non-human primates. Proc Natl Acad Sci USA 100: 15953–15958PubMedCrossRefGoogle Scholar
  38. Rathinavelu S, de Silva AM (2001) Purification and characterization of Borrelia burgdorferi from feeding nymphal ticks (Ixodes scapularis). Infect Immun 69: 3536–3541PubMedCrossRefGoogle Scholar
  39. Seshu J, Boylan JA, Gherardini FC, Skare JT (2004) Dissolved oxygen levels alter gene expression and antigen profiles in Borrelia burgdorferi. Infect Immun 72: 1580–1586PubMedCrossRefGoogle Scholar
  40. Templeton TJ (2004) Borrelia outer membrane surface proteins and transmission through the tick. J Exp Med 199: 603–606PubMedCrossRefGoogle Scholar
  41. Yang X, Popova TG, Hagman KE, Wikel SK, Schoeler GB, Caimano MJ, et al (1999) Identification, characterization, and expression of three new members of the Borrelia burgdorferi Mlp (2.9) lipoprotein gene family. Infect Immun 67: 6008–6018PubMedGoogle Scholar
  42. Yang X, Goldberg MS, Popova TG, Schoeler GB, Wikel SK, Hagman KE, et al (2000) Interdependence of environmental factors influencing reciprocal patterns of gene expression in virulent Borrelia burgdorferi. Mol Microbiol 37: 1470–1479PubMedCrossRefGoogle Scholar
  43. Yang XF, Hübner A, Popova TG, Hagman KE, Norgard MV (2003) Regulation of expression of the paralogous Mlp family in Borrelia burgdorferi. Infect Immun 71: 5012–5020PubMedCrossRefGoogle Scholar
  44. Yang XF, Alani SM, Norgard MV (2003) The response regulator Rrp2 is essential for the expression of major membrane lipoproteins in Borrelia burgdorferi. Proc Natl Acad Sci USA 100: 11001–11006PubMedCrossRefGoogle Scholar
  45. Fingerle V, Liegl G, Munderloh U, Wilske B (1998) Expression of outer surface proteins A and C of Borrelia burgdorferi in Ixodes ricinus ticks removed from humans. Med Microbiol Immunol 187: 121–126PubMedCrossRefGoogle Scholar
  46. Fingerle V, Laux H, Munderloh UG, Schulte-Spechtel U, Wilske B (2000) Differential expression of outer surface proteins A and C by individual Borrelia burgdorferi in different genospecies. Med Microbiol Immunol 189: 59–66PubMedCrossRefGoogle Scholar
  47. Caimano MJ, Eggers CH, Gonzalez CA, Radolf JD (2005) Alternate sigma factor RpoS is required for the in vivo-specific repression of Borrelia burgdorferi plasmid lp45-borne ospA and lp6.6 genes. J Bacteriol 187: 7845–7852PubMedCrossRefGoogle Scholar
  48. Hübner A, Yang X, Nolen DM, Popova TG, Cabello PC, Norgard MV (2001) Expression of Borrelia burgdorferi OspC and DbpA is controlled by a RpoN-RpoS regulatory pathway. Proc Natl Acad Sci USA 98: 12724–12729PubMedCrossRefGoogle Scholar
  49. Yang XF, Lybecker MC, Pal U, Alani SM, Blevins J, Revel AT, et al (2005) Analysis of the ospC regulatory element controlled by the RpoN-RpoS regulatory pathway in Borrelia burgdorferi. J Bacteriol 187: 4822–4829PubMedCrossRefGoogle Scholar
  50. Carroll JA, Garon CF, Schwan TG (1999) Effects of environmental pH on membrane proteins in Borrelia burgdorferi. Infect Immun 67: 3181–3187PubMedGoogle Scholar
  51. Carroll JA, Cordova RM, Garon CF (2000) Identification of eleven pH-regulated genes in Borrelia burgdorferi localized to linear plasmids. Infect Immun 68: 6677–6684PubMedCrossRefGoogle Scholar
  52. Carroll JA, El-Hage N, Miller JC, Babb K, Stevenson B (2001) Borrelia burgdorferi RevA antigen is a surfaceexposed outer membrane protein whose expression is regulated in response to environmental temperature and pH. Infect Immun 69: 5286–5293PubMedCrossRefGoogle Scholar
  53. Indest KJ, Ramamoorthy R, Sole M, Gilmore RD Jr, Johnson BJB, Philipp MT (1997) Cell-density-dependent expression of Borrelia burgdorferi lipoproteins in vitro. Infect Immun 65: 1165–1171PubMedGoogle Scholar
  54. Ramamoorthy R, Philipp MT (1998) Differential expression of Borrelia burgdorferi proteins during growth in vitro. Infect Immun 66: 5119–5124PubMedGoogle Scholar
  55. Ramamoorthy R, Scholl-Meeker D (2001) Borrelia burgdorferi proteins whose expression is similarly affected by culture temperature and pH. Infect Immun 69: 2739–2742PubMedCrossRefGoogle Scholar
  56. Yang X, Popova TG, Goldberg MS, Norgard MV (2001) Influence of cultivation media on genetic regulatory patterns in Borrelia burgdorferi. Infect Immun 69: 4159–4163PubMedCrossRefGoogle Scholar
  57. Obonyo M, Munderloh UG, Fingerle V, Wilske B, Kurtti TJ (1999) Borrelia burgdorferi in tick cell culture modulates expression of outer surface proteins A and C in response to temperature. J Clin Microbiol 37: 2137–2141PubMedGoogle Scholar
  58. Stevenson B, Zückert WR, Akins DR (2001) Repetition, conservation, and variation: the multiple cp32 plasmids of Borrelia species. In: Saier MH, García-Lara J (eds) The spirochetes: molecular and cellular biology. Horizon Press, Oxford, pp 87–100Google Scholar
  59. Stevenson B, Babb K, Bykowski T, Cooley AE, Woodman ME, von Lackum K, et al (2006) The Lyme disease spirochete Erp lipoprotein family: structure, function and regulation of expression. In: Cabello FC, Godfrey HP, Hulinska D (eds) Molecular biology of spirochetes. IOS Press, Amsterdam (in press)Google Scholar
  60. Akins DR, Porcella SF, Popova TG, Shevchenko D, Baker SI, Li M, et al (1995) Evidence for in vivo but not in vitro expression of a Borrelia burgdorferi outer surface protein F (OspF) homologue. Mol Microbiol 18: 507–520PubMedCrossRefGoogle Scholar
  61. Babb K, El-Hage N, Miller JC, Carroll JA, Stevenson B (2001) Distinct regulatory pathways control the synthesis of Borrelia burgdorferi infection-associated OspC and Erp surface proteins. Infect Immun 69: 4146–4153PubMedCrossRefGoogle Scholar
  62. Babb K, McAlister JD, Miller JC, Stevenson B (2004) Molecular characterization of Borrelia burgdorferi erp promoter/operator elements. J Bacteriol 186: 2745–2756PubMedCrossRefGoogle Scholar
  63. Caimano MJ, Eggers CH, Hazlett KRO, Radolf JD (2004) RpoS is not central to the general stress response in Borrelia burgdorferi but does control expression of one or more essential virulence determinants. Infect Immun 72: 6433–6445PubMedCrossRefGoogle Scholar
  64. Das S, Barthold SW, Stocker Giles S, Montgomery RR, Telford SR, Fikrig E (1997) Temporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host. J Clin Invest 99: 987–995PubMedCrossRefGoogle Scholar
  65. Eggers CH, Caimano MJ, Radolf JD (2004) Analysis of promoter elements involved in the transcription initiation of RpoS-dependent Borrelia burgdorferi genes. J Bacteriol 186: 7390–7402PubMedCrossRefGoogle Scholar
  66. El-Hage N, Stevenson B (2002) Simultaneous coexpression of Borrelia burgdorferi Erp proteins occurs through a specific, erp locus-directed regulatory mechanism. J Bacteriol 184: 4536–4543PubMedCrossRefGoogle Scholar
  67. Gilmore RD Jr, Mbow ML, Stevenson B (2001) Analysis of Borrelia burgdorferi gene expression during life cycle phases of the tick vector Ixodes scapularis. Microbes Infect 3: 799–808PubMedCrossRefGoogle Scholar
  68. Hefty PS, Jolliff SE, Caimano MJ, Wikel SK, Radolf JD, Akins DR (2001) Regulation of OspE-related, OspF-related, and Elp lipoproteins of Borrelia burgdorferi strain 297 by mammalian host-specific signals. Infect Immun 69: 3618–3627PubMedCrossRefGoogle Scholar
  69. Hefty PS, Jolliff SE, Caimano MJ, Wikel SK, Akins DR (2002) Changes in the temporal and spatial patterns of outer surface lipoprotein expression generate population heterogeneity and antigenic diversity in the Lyme disease spirochete, Borrelia burgdorferi. Infect Immun 70: 3468–3478PubMedCrossRefGoogle Scholar
  70. Kraiczy P, Skerka C, Brade V, Zipfel PF (2001) Further characterization of complement regulator-acquiring surface proteins of Borrelia burgdorferi. Infect Immun 69: 7800–7809PubMedCrossRefGoogle Scholar
  71. McDowell JV, Sung SY, Price G, Marconi RT (2001) Demonstration of the genetic stability and temporal expression of select members of the Lyme disease spirochete OspF protein family during infection in mice. Infect Immun 69: 4831–4838PubMedCrossRefGoogle Scholar
  72. Miller JC, Stevenson B (2004) Increased expression of Borrelia burgdorferi factor H-binding surface proteins during transmission from ticks to mice. Int J Med Microbiol 293 S37: 120–125PubMedGoogle Scholar
  73. Miller JC, Narayan K, Stevenson B, Pachner AR (2005) Expression of Borrelia burgdorferi erp genes during infection of non-human primates. Microb Pathog 39: 27–33PubMedCrossRefGoogle Scholar
  74. Stevenson B, Bono JL, Schwan TG, Rosa P (1998) Borrelia burgdorferi Erp proteins are immunogenic in mammals infected by tick bite, and their synthesis is inducible in cultured bacteria. Infect Immun 66: 2648–2654PubMedGoogle Scholar
  75. Wallich R, Brenner C, Kramer MD, Simon MM (1995) Molecular cloning and immunological characterization of a novel linear-plasmid-encoded gene, pG, of Borrelia burgdorferi expressed only in vivo. Infect Immun 63: 3327–3335PubMedGoogle Scholar
  76. Crother TR, Champion CI, Whitelegge JP, Aguilera R, Wu XY, Blanco DR, et al (2004) Temporal analysis of the antigenic composition of Borrelia burgdorferi during infection in rabbit skin. Infect Immun 72: 5063–5072PubMedCrossRefGoogle Scholar
  77. Liang FT, Jacobs MB, Bowers LC, Philipp MT (2002) An immune evasion mechanism for spirochetal persistence in Lyme borreliosis. J Exp Med 195: 415–422PubMedCrossRefGoogle Scholar
  78. Liang FT, Yan J, Mbow ML, Sviat SL, Gilmore RD, Mamula M, et al (2004) Borrelia burgdorferi changes its surface antigenic expression in response to host immune responses. Infect Immun 72: 5759–5767PubMedCrossRefGoogle Scholar
  79. Miller JC, Stevenson B (2006) Borrelia burgdorferi erp genes are expressed at different levels within tissues of chronically infected mammalian hosts. Int J Med Microbiol 296 (51): 185–194PubMedCrossRefGoogle Scholar
  80. Alitalo A, Meri T, Lankinen H, Seppälä I, Lahdenne P, Hefty PS, et al (2002) Complement inhibitor factor H binding to Lyme disease spirochetes is mediated by inducible expression of multiple plasmid-encoded outer surface protein E paralogs. J Immunol 169: 3847–3853PubMedGoogle Scholar
  81. Hellwage J, Meri T, Heikkilä T, Alitalo A, Panelius J, Lahdenne P, et al (2001) The complement regulatory factor H binds to the surface protein OspE of Borrelia burgdorferi. J Biol Chem 276: 8427–8435PubMedCrossRefGoogle Scholar
  82. Kraiczy P, Hellwage J, Skerka C, Kirschfink M, Brade V, Zipfel PF, et al (2003) Immune evasion of Borrelia burgdorferi: mapping of a complement inhibitor factor H-binding site of BbCRASP-3, a novel member of the Erp protein family. Eur J Immunol 33: 697–707PubMedCrossRefGoogle Scholar
  83. Kraiczy P, Hartmann K, Hellwage J, Skerka C, Brade V, Zipfel PF, et al (2004) Immunological characterization of the complement regulator factor H-binding CRASP and Erp proteins of Borrelia burgdorferi. Int J Med Microbiol 293 (S37): 152–157PubMedGoogle Scholar
  84. Metts MS, McDowell JV, Theisen M, Hansen PR, Marconi RT (2003) Analysis of the OspE determinants involved in binding of factor H and OspE-targeting antibodies elicited during Borrelia burgdorferi infection. Infect Immun 71: 3587–3596PubMedCrossRefGoogle Scholar
  85. Stevenson B, El-Hage N, Hines MA, Miller JC, Babb K (2002) Differential binding of host complement inhibitor factor H by Borrelia burgdorferi Erp surface proteins: a possible mechanism underlying the expansive host range of Lyme disease spirochetes. Infect Immun 70: 491–497PubMedCrossRefGoogle Scholar
  86. Lawrie CH, Randolph SE, Nuttall PA (1999) Ixodes ticks: serum species sensitivity of anticomplement activity. Exp Parasitol 93: 207–214PubMedCrossRefGoogle Scholar
  87. Rathinavelu S, Broadwater A, de Silva AM (2003) Does host complement kill Borrelia burgdorferi within ticks? Infect Immun 71: 822–829PubMedCrossRefGoogle Scholar
  88. Ribeiro JMC (1987) Ixodes dammini: salivary anti-complement activity. Exp Parasitol 64: 347–353PubMedCrossRefGoogle Scholar
  89. Valenzuela JG, Charlab R, Mathers TN, Ribeiro JMC (2000) Purification, cloning, and expression of a novel salivary anticomplement protein from the tick, Ixodes scapularis. J Biol Chem 275: 18717–18723PubMedCrossRefGoogle Scholar
  90. Brooks CS, Vuppala SR, Jett AM, Alitalo A, Meri S, Akins DR (2005) Complement regulator-acquiring surface protein 1 imparts resistance to human serum in Borrelia burgdorferi. J Immunol 175: 3299–3308PubMedGoogle Scholar
  91. Cordes FS, Roversi P, Kraiczy P, Simon MM, Brade V, Jahraus O, et al (2005) A novel fold for factor H-binding protein BbCRASP-1 of Borrelia burgdorferi. Nature Struct Mol Biol 12: 276–277CrossRefGoogle Scholar
  92. Kraiczy P, Hellwage J, Skerka C, Becker H, Kirschfink M, Simon MM, et al (2004) Complement resistance of Borrelia burgdorferi correlates with the expression of BbCRASP-1, a novel linear plasmid-encoded surface protein that interacts with human factor H and FHL-1 and is unrelated to Erp proteins. J Biol Chem 279: 2421–2429PubMedCrossRefGoogle Scholar
  93. McDowell JV, Harlin ME, Rogers EA, Marconi RT (2005) Putative coiled-coil structural elements of the BBA68 protein of Lyme disease spirochetes are required for formation of its factor H binding site. J Bacteriol 187: 1317–1323PubMedCrossRefGoogle Scholar
  94. von Lackum K, Miller JC, Bykowski T, Riley SP, Woodman ME, Brade V, et al (2005) Borrelia burgdorferi regulates expression of complement regulator-acquiring surface protein 1 during the mammal-tick infection cycle. Infect Immun 73: 7398–7405PubMedCrossRefGoogle Scholar
  95. Wallich R, Pattathu J, Kitiratschky V, Brenner C, Zipfel PF, Brade V, et al (2005) Identification and functional characterization of complement regulator-acquiring surface protein 1 of the Lyme disease spirochetes Borrelia afzelii and Borrelia garinii. Infect Immun 73: 2351–2359PubMedCrossRefGoogle Scholar
  96. Wallich R, Zipfel PF, Skerka C, Kirschfink M, Simon MM, Stevenson B, et al (2006) Lyme disease spirochetes evade innate immunity by acquisition of complement regulators. In: Cabello FC, Godfrey HP, Hulinska D (eds) Molecular biology of spirochetes. IOS Press, Amsterdam (in press)Google Scholar
  97. Lederer S, Brenner C, Stehle T, Gern L, Wallich R, Simon MM (2005) Quantitative analysis of Borrelia burgdorferi gene expression in naturally (tick) infected mouse strains. Med Microbiol Immunol 194: 81–90PubMedCrossRefGoogle Scholar
  98. Wallich R, Jahraus O, Stehle T, Tran TTT, Brenner C, Hofmann H, et al (2003) Artificial-infection protocols allow immunodetection of novel Borrelia burgdorferi antigens suitable as vaccine candidates against Lyme disease. Eur J Immunol 33: 708–719PubMedCrossRefGoogle Scholar
  99. Ledin KE, Zeidner NS, Ribeiro JM, Biggerstaff BJ, Dolan MC, Dietrich G, et al (2005) Borreliacidal activity of saliva of the tick Amblyomma americanum. Med Vet Entomol 19: 90–95PubMedCrossRefGoogle Scholar
  100. Sauer JR, McSwain JL, Bowman AS, Essenberg RC (1995) Tick salivary gland physiology. Ann Rev Entomol 40: 245–267CrossRefGoogle Scholar
  101. Iyer R, Hardham JM, Wormser GP, Schwartz I, Norris SJ (2000) Conservation and heterogeneity of vlsE among human and tick isolates of Borrelia burgdorferi. Infect Immun 68: 1714–1718PubMedCrossRefGoogle Scholar
  102. Kawabata H, Myouga F, Inagaki Y, Murai N, Watanabe H (1998) Genetic and immunological analyses of Vls (VMP-like sequences) of Borrelia burgdorferi. Microb Pathog 24: 155–166PubMedCrossRefGoogle Scholar
  103. Wang D, Botkin DJ, Norris SJ (2003) Characterization of the vls antigenic variation loci of the Lyme disease spirochaetes Borrelia garinii Ip90 and Borrelia afzelii ACA1. Mol Microbiol 47: 1407–1417PubMedCrossRefGoogle Scholar
  104. Wang G, van Dam AP, Dankert J (2001) Analysis of a VMP-like sequence (vls) locus in Borrelia garinii and Vls homologues among four Borrelia burgdorferi sensu lato species. FEMS Microbiol Lett 199: 39–45PubMedCrossRefGoogle Scholar
  105. Zhang J-R, Hardham JM, Barbour AG, Norris SJ (1997) Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes. Cell 89: 1–20CrossRefGoogle Scholar
  106. Zhang J-R, Norris SJ (1998) Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion. Infect Immun 66: 3698–3704PubMedGoogle Scholar
  107. Zhang J-R, Norris SJ (1998) Kinetics and in vivo induction of genetic variation of vlsE in Borrelia burgdorferi. Infect Immun 66: 3689–3697PubMedGoogle Scholar
  108. Anguita J, Thomas V, Samanta S, Persinski R, Hernanz C, Barthold SW, et al (2001) Borrelia burgdorferi-induced inflammation facilitates spirochete adaptation and variable major protein-like sequence locus recombination. J Immunol 167: 3383–3390PubMedGoogle Scholar
  109. Indest KJ, Howell JK, Jacobs MB, Scholl-Meeker D, Norris SJ, Philipp MT (2001) Analysis of Borrelia burgdorferi vlsE gene expression and recombination in the tick vector. Infect Immun 69: 7083–7090PubMedCrossRefGoogle Scholar
  110. Ohnishi J, Schneider B, Messer WB, Piesman J, deSilva AM (2003) Genetic variation at the vlsE locus of Borrelia burgdorferi within ticks and mice over the course of a single transmission cycle. J Bacteriol 185: 4432–4441PubMedCrossRefGoogle Scholar
  111. Bykowski T, Babb K, von Lackum K, Riley SP, Norris SJ, Stevenson B (2006) Transcriptional regulation of the Borrelia burgdorferi antigenically variable VlsE surface protein during the mammal-tick infectious cycle. J Bacteriol 188: 4879–4889PubMedCrossRefGoogle Scholar
  112. Lawrenz MB, Hardham JM, Owens RT, Nowakowski J, Steere AC, Wormser GP, et al (1999) Human antibody responses to VlsE antigenic variation protein of Borrelia burgdorferi. J Clin Microbiol 37: 3997–4004PubMedGoogle Scholar
  113. Liang FT, Alvarez AL, Gu Y, Nowling JM, Ramamoorthy R, Philipp MT (1999) An immunodominant conserved region within the variable domain of VlsE, the variable surface antigen of Borrelia burgdorferi. J Immunol 163: 5566–5573PubMedGoogle Scholar
  114. de Silva AM, Fikrig E (1995) Growth and migration of Borrelia burgdorferi in Ixodes ticks during blood feeding. Am J Trop Med Hyg 53: 397–404PubMedGoogle Scholar
  115. Piesman J, Schneider BS (2002) Dynamic changes in Lyme disease spirochetes during transmission by nymphal ticks. Exp Appl Acarol 28: 141–145PubMedCrossRefGoogle Scholar
  116. Piesman J, Schneider BS, Zeidner NS (2001) Use of quantitative PCR to measure density of Borrelia burgdorferi in the midgut and salivary glands of feeding tick vectors. J Clin Microbiol 39: 4145–4148PubMedCrossRefGoogle Scholar
  117. Piesman J, Oliver JR, Sinsky RJ (1990) Growth kinetics of the Lyme disease spirochete (Borrelia burgdorferi) in vector ticks (Ixodes dammini). Am J Trop Med Hyg 42: 352–357PubMedGoogle Scholar
  118. Casjens S, Palmer N, van Vugt R, Huang WM, Stevenson B, Rosa P, et al (2000) A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs of an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi. Mol Microbiol 35: 490–516PubMedCrossRefGoogle Scholar
  119. Fraser CM, Casjens S, Huang WM, Sutton GG, Clayton R, Lathigra R, et al (1997) Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390: 580–586PubMedCrossRefGoogle Scholar
  120. Bugrysheva J, Dobrikova EY, Godfrey HP, Sartakova ML, Cabello FC (2002) Modulation of Borrelia burgdorferi stringent response and gene expression during extracellular growth with tick cells. Infect Immun 70: 3061–3067PubMedCrossRefGoogle Scholar
  121. Bugrysheva J, Dobrikova EY, Sartakova ML, Caimano MJ, Daniels TJ, Radolf JD, et al (2003) Characterization of the stringent response and rel Bbu expression in Borrelia burgdorferi. J Bacteriol 185: 957–965PubMedCrossRefGoogle Scholar
  122. Bugrysheva JV, Bruyskin AV, Godfrey HP, Cabello FC (2005) Borrelia burgdorferi rel is responsible for generation of guanosine-3′-diphosphate-5′-triphosphate and growth control. Infect Immun 73: 4972–4981PubMedCrossRefGoogle Scholar
  123. Concepcion MB, Nelson DR (2003) Expression of spoT in Borrelia burgdorferi during serum starvation. J Bacteriol 185: 444–452PubMedCrossRefGoogle Scholar
  124. Babb K, von Lackum K, Wattier RL, Riley SP, Stevenson B (2005) Synthesis of autoinducer 2 by the Lyme disease spirochete, Borrelia burgdorferi. J Bacteriol 187: 3079–3087PubMedCrossRefGoogle Scholar
  125. Ryjenkov DA, Tarutina M, Moskvin OV, Gomelsky M (2005) Cyclic diguanylate is a ubiquitous signaling molecule in bacteria: insights into biochemistry of the GGDEF protein domain. J Bacteriol 187: 1792–1798PubMedCrossRefGoogle Scholar
  126. Stevenson B, Babb K (2002) LuxS-mediated quorum sensing in Borrelia burgdorferi, the Lyme disease spirochete. Infect Immun 70: 4099–4105PubMedCrossRefGoogle Scholar
  127. von Lackum K, Babb K, Riley SP, Wattier RL, Bykowski T, Stevenson B (2006) Functionality of Borrelia burgdorferi LuxS: the Lyme disease spirochete produces and responds to the pheromone autoinducer-2, and lacks a complete activated-methyl cycle. Int J Med Microbiol 296 (51): 92–102PubMedCrossRefGoogle Scholar
  128. Boylan JA, Posey JE, Gherardini FC (2003) Borrelia oxidative stress response regulator, BosR: a distinct Zndependent transcriptional activator. Proc Natl Acad Sci USA 100: 11684–11689PubMedCrossRefGoogle Scholar
  129. Katona LI, Tokarz R, Kuhlow CJ, Benach J, Benach JL (2004) The Fur homologue in Borrelia burgdorferi. J Bacteriol 186: 6443–6456PubMedCrossRefGoogle Scholar
  130. Babb K, Bykowski T, Riley SP, Miller MC, DeMoll E, Stevenson B (2006) Borrelia burgdorferi EbfC, a novel, chromosomally-encoded protein, binds specific DNA sequences adjacent to erp loci on the spirochete's resident cp32 prophages. J Bacteriol 188: 4331–4339PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Brian Stevenson
    • 1
  • Kate von Lackum
    • 1
  • Sean P. Riley
    • 1
  • Anne E. Cooley
    • 1
  • Michael E. Woodman
    • 1
  • Tomasz Bykowski
    • 1
  1. 1.Department of Microbiology, Immunology, and Molecular GeneticsUniversity of Kentucky College of Medicine, MS 415 Chandler Medical CenterLexingtonU.S.A

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