1887

Abstract

The surface lipoproteins of the Lyme disease spirochaete directly interact with tissue microenvironments during mammalian infection, and thus potentially affect various aspects of infection. To investigate the influence of surface antigen synthesis on infectious behaviour, was modified to constitutively produce the well-characterized surface lipoproteins OspA and invariant VlsE. Although increasing OspA or VlsE production did not significantly affect synthesis of other surface lipoproteins or spirochaetal growth , overexpressing resulted in increased but decreased expression, and overexpressing led to decreased and expression in severe combined immunodeficient (SCID) mice. Increasing the expression of either or did not alter the ID, but affected spirochaetal dissemination and significantly reduced tissue spirochaete loads in SCID mice. In immunocompetent mice, increased expression resulted in quick clearance of infection, while constitutive expression led to a substantial ID increase and severely impaired dissemination. Furthermore, with constitutive expression persisted in the skin tissue but was cleared from both heart and joints of chronically infected immunocompetent mice. Taken together, the study indicates that increasing production of OspA or invariant VlsE influences lipoprotein gene expression in the murine host and alters the infectious behaviour of .

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2008-11-01
2019-10-14
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References

  1. Bankhead, T. & Chaconas, G. ( 2007; ). The role of VlsE antigenic variation in the Lyme disease spirochete: persistence through a mechanism that differs from other pathogens. Mol Microbiol 65, 1547–1558.[CrossRef]
    [Google Scholar]
  2. Bykowski, T., Woodman, M. E., Cooley, A. E., Brissette, C. A., Brade, V., Wallich, R., Kraiczy, P. & Stevenson, B. ( 2007; ). Coordinated expression of Borrelia burgdorferi complement regulator-acquiring surface proteins during the Lyme disease spirochete's mammal-tick infection cycle. Infect Immun 75, 4227–4236.[CrossRef]
    [Google Scholar]
  3. Coleman, J. L., Sellati, T. J., Testa, J. E., Kew, R. R., Furie, M. B. & Benach, J. L. ( 1995; ). Borrelia burgdorferi binds plasminogen, resulting in enhanced penetration of endothelial monolayers. Infect Immun 63, 2478–2484.
    [Google Scholar]
  4. Coleman, J. L., Gebbia, J. A., Piesman, J., Degen, J. L., Bugge, T. H. & Benach, J. L. ( 1997; ). Plasminogen is required for efficient dissemination of B. burgdorferi in ticks and for enhancement of spirochetemia in mice. Cell 89, 1111–1119.[CrossRef]
    [Google Scholar]
  5. Coleman, J. L., Roemer, E. J. & Benach, J. L. ( 1999; ). Plasmin-coated Borrelia burgdorferi degrades soluble and insoluble components of the mammalian extracellular matrix. Infect Immun 67, 3929–3936.
    [Google Scholar]
  6. Crother, T. R., Champion, C. I., Wu, X. Y., Blanco, D. R., Miller, J. N. & Lovett, M. A. ( 2003; ). Antigenic composition of Borrelia burgdorferi during infection of SCID mice. Infect Immun 71, 3419–3428.[CrossRef]
    [Google Scholar]
  7. Crother, T. R., Champion, C. I., Whitelegge, J. P., Aguilera, R., Wu, X. Y., Blanco, D. R., Miller, J. N. & Lovett, M. A. ( 2004; ). Temporal analysis of the antigenic composition of Borrelia burgdorferi during infection in rabbit skin. Infect Immun 72, 5063–5072.[CrossRef]
    [Google Scholar]
  8. de Silva, A. M., Telford, S. R., III, Brunet, L. R., Barthold, S. W. & Fikrig, E. ( 1996; ). Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine. J Exp Med 183, 271–275.[CrossRef]
    [Google Scholar]
  9. de Silva, A. M., Fish, D., Burkot, T. R., Zhang, Y. & Fikrig, E. ( 1997; ). OspA antibodies inhibit the acquisition of Borrelia burgdorferi by Ixodes ticks. Infect Immun 65, 3146–3150.
    [Google Scholar]
  10. Fingerle, V., Goettner, G., Gern, L., Wilske, B. & Schulte-Spechtel, U. ( 2007; ). Complementation of a Borrelia afzelii OspC mutant highlights the crucial role of OspC for dissemination of Borrelia afzelii in Ixodes ricinus. Int J Med Microbiol 297, 97–107.[CrossRef]
    [Google Scholar]
  11. Fuchs, H., Wallich, R., Simon, M. M. & Kramer, M. D. ( 1994; ). The outer surface protein A of the spirochete Borrelia burgdorferi is a plasmin(ogen) receptor. Proc Natl Acad Sci U S A 91, 12594–12598.[CrossRef]
    [Google Scholar]
  12. Fung, B. P., McHugh, G. L., Leong, J. M. & Steere, A. C. ( 1994; ). 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 62, 3213–3221.
    [Google Scholar]
  13. Gilmore, R. D., 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, 411–414.[CrossRef]
    [Google Scholar]
  14. Gilmore, R. D., Jr, Howison, R. R., Schmit, V. L., Nowalk, A. J., Clifton, D. R., Nolder, C., Hughes, J. L. & Carroll, J. A. ( 2007; ). Temporal expression analysis of the Borrelia burgdorferi paralogous gene family 54 genes BBA64, BBA65, and BBA66 during persistent infection in mice. Infect Immun 75, 2753–2764.[CrossRef]
    [Google Scholar]
  15. Grimm, D., Tilly, K., Byram, R., Stewart, P. E., Krum, J. G., Bueschel, D. M., Schwan, T. G., Policastro, P. F., Elias, A. F. & Rosa, P. A. ( 2004; ). Outer-surface protein C of the Lyme disease spirochete: a protein induced in ticks for infection of mammals. Proc Natl Acad Sci U S A 101, 3142–3147.[CrossRef]
    [Google Scholar]
  16. Hu, L. T., Perides, G., Noring, R. & Klempner, M. S. ( 1995; ). Binding of human plasminogen to Borrelia burgdorferi. Infect Immun 63, 3491–3496.
    [Google Scholar]
  17. Hubner, A., Yang, X., Nolen, D. M., Popova, T. G., Cabello, F. C. & Norgard, M. V. ( 2001; ). Expression of Borrelia burgdorferi OspC and DbpA is controlled by a RpoN–RpoS regulatory pathway. Proc Natl Acad Sci U S A 98, 12724–12729.[CrossRef]
    [Google Scholar]
  18. Klempner, M. S., Noring, R., Epstein, M. P., McCloud, B. & Rogers, R. A. ( 1996; ). Binding of human urokinase type plasminogen activator and plasminogen to Borrelia species. J Infect Dis 174, 97–104.[CrossRef]
    [Google Scholar]
  19. Lagal, V., Portnoi, D., Faure, G., Postic, D. & Baranton, G. ( 2006; ). Borrelia burgdorferi sensu stricto invasiveness is correlated with OspC-plasminogen affinity. Microbes Infect 8, 645–652.[CrossRef]
    [Google Scholar]
  20. Lawrenz, M. B., Wooten, R. M. & Norris, S. J. ( 2004; ). Effects of vlsE complementation on the infectivity of Borrelia burgdorferi lacking the linear plasmid lp28-1. Infect Immun 72, 6577–6585.[CrossRef]
    [Google Scholar]
  21. Liang, F. T., Jacobs, M. B., Bowers, L. C. & Philipp, M. T. ( 2002a; ). An immune evasion mechanism for spirochetal persistence in Lyme borreliosis. J Exp Med 195, 415–422.[CrossRef]
    [Google Scholar]
  22. Liang, F. T., Nelson, F. K. & Fikrig, E. ( 2002b; ). Molecular adaptation of Borrelia burgdorferi in the murine host. J Exp Med 196, 275–280.[CrossRef]
    [Google Scholar]
  23. Liang, F. T., Caimano, M. J., Radolf, J. D. & Fikrig, E. ( 2004a; ). Borrelia burgdorferi outer surface protein (osp) B expression independent of ospA. Microb Pathog 37, 35–40.[CrossRef]
    [Google Scholar]
  24. Liang, F. T., Yan, J., Mbow, M. L., Sviat, S. L., Gilmore, R. D., Mamula, M. & Fikrig, E. ( 2004b; ). Borrelia burgdorferi changes its surface antigenic expression in response to host immune responses. Infect Immun 72, 5759–5767.[CrossRef]
    [Google Scholar]
  25. Neelakanta, G., Li, X., Pal, U., Liu, X., Beck, D. S., Deponte, K., Fish, D., Kantor, F. S. & Fikrig, E. ( 2007; ). Outer surface protein B is critical for Borrelia burgdorferi adherence and survival within Ixodes ticks. PLoS Pathog 3, e33 [CrossRef]
    [Google Scholar]
  26. Ohnishi, J., Piesman, J. & de Silva, A. M. ( 2001; ). Antigenic and genetic heterogeneity of Borrelia burgdorferi populations transmitted by ticks. Proc Natl Acad Sci U S A 98, 670–675.[CrossRef]
    [Google Scholar]
  27. Pal, U., Yang, X., Chen, M., Bockenstedt, L. K., Anderson, J. F., Flavell, R. A., Norgard, M. V. & Fikrig, E. ( 2004; ). OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands. J Clin Invest 113, 220–230.[CrossRef]
    [Google Scholar]
  28. Purser, J. E., Lawrenz, M. B., Caimano, M. J., Howell, J. K., Radolf, J. D. & Norris, S. J. ( 2003; ). A plasmid-encoded nicotinamidase (PncA) is essential for infectivity of Borrelia burgdorferi in a mammalian host. Mol Microbiol 48, 753–764.[CrossRef]
    [Google Scholar]
  29. Schwan, T. G. & 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, 382–388.
    [Google Scholar]
  30. Schwan, T. G., Piesman, J., Golde, W. T., Dolan, M. C. & Rosa, P. A. ( 1995; ). Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc Natl Acad Sci U S A 92, 2909–2913.[CrossRef]
    [Google Scholar]
  31. Stewart, P. E., Wang, X., Bueschel, D. M., Clifton, D. R., Grimm, D., Tilly, K., Carroll, J. A., Weis, J. J. & Rosa, P. A. ( 2006; ). Delineating the requirement for the Borrelia burgdorferi virulence factor OspC in the mammalian host. Infect Immun 74, 3547–3553.[CrossRef]
    [Google Scholar]
  32. Strother, K. O., Hodzic, E., Barthold, S. W. & de Silva, A. M. ( 2007; ). Infection of mice with Lyme disease spirochetes constitutively producing outer surface proteins A and B. Infect Immun 75, 2786–2794.[CrossRef]
    [Google Scholar]
  33. Tilly, K., Krum, J. G., Bestor, A., Jewett, M. W., Grimm, D., Bueschel, D., Byram, R., Dorward, D., Vanraden, M. J. & other authors ( 2006; ). Borrelia burgdorferi OspC protein required exclusively in a crucial early stage of mammalian infection. Infect Immun 74, 3554–3564.[CrossRef]
    [Google Scholar]
  34. Tsao, J., Barbour, A. G., Luke, C. J., Fikrig, E. & Fish, D. ( 2001; ). OspA immunization decreases transmission of Borrelia burgdorferi spirochetes from infected Peromyscus leucopus mice to larval Ixodes scapularis ticks. Vector Borne Zoonotic Dis 1, 65–74.[CrossRef]
    [Google Scholar]
  35. Tsao, J. I., Wootton, J. T., Bunikis, J., Luna, M. G., Fish, D. & Barbour, A. G. ( 2004; ). An ecological approach to preventing human infection: vaccinating wild mouse reservoirs intervenes in the Lyme disease cycle. Proc Natl Acad Sci U S A 101, 18159–18164.[CrossRef]
    [Google Scholar]
  36. Xu, Q., Seemanapalli, S. V., Lomax, L., McShan, K., Li, X., Fikrig, E. & Liang, F. T. ( 2005; ). Association of linear plasmid 28-1 with an arthritic phenotype of Borrelia burgdorferi. Infect Immun 73, 7208–7215.[CrossRef]
    [Google Scholar]
  37. Xu, Q., Seemanapalli, S. V., McShan, K. & Liang, F. T. ( 2006; ). Constitutive expression of outer surface protein C diminishes the ability of Borrelia burgdorferi to evade specific humoral immunity. Infect Immun 74, 5177–5184.[CrossRef]
    [Google Scholar]
  38. Xu, Q., McShan, K. & Liang, F. T. ( 2007a; ). Identification of an ospC operator critical for immune evasion of Borrelia burgdorferi. Mol Microbiol 64, 220–231.[CrossRef]
    [Google Scholar]
  39. Xu, Q., Seemanaplli, S. V., McShan, K. & Liang, F. T. ( 2007b; ). Increasing the interaction of Borrelia burgdorferi with decorin significantly reduces the 50 percent infectious dose and severely impairs dissemination. Infect Immun 75, 4272–4281.[CrossRef]
    [Google Scholar]
  40. Xu, Q., McShan, K. & Liang, F. T. ( 2008; ). Essential protective role attributed to the surface lipoproteins of Borrelia burgdorferi against innate defences. Mol Microbiol 69, 15–29.[CrossRef]
    [Google Scholar]
  41. Yang, X. F., Pal, U., Alani, S. M., Fikrig, E. & Norgard, M. V. ( 2004; ). Essential role for OspA/B in the life cycle of the Lyme disease spirochete. J Exp Med 199, 641–648.[CrossRef]
    [Google Scholar]
  42. Zhang, J. R., Hardham, J. M., Barbour, A. G. & Norris, S. J. ( 1997; ). Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes. Cell 89, 275–285.[CrossRef]
    [Google Scholar]
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vol. , part 11, pp. 3420 - 3429

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