1887

Abstract

During cycling between the tick vector and a mammal, the Lyme disease spirochaete must coordinate expression of outer-surface proteins (Osps) A and B to quickly respond to environmental changes. The pathogen abundantly produces OspA/B in the tick, but represses their expression during mammalian infection. This paper reports a regulatory structure, consisting of two sequences flanking the promoter, that is required for enhancing expression in grown , but repressing its expression during murine infection. Deletion or replacement of either the upstream or downstream sequence of the promoter caused a significant decrease in expression , but a dramatic increase during murine infection. Fusion of either sequence with the reporter promoter led to increased expression of an reporter gene , but a decrease in the murine host. Furthermore, simultaneous fusion of both sequences with the reporter promoter showed a synergistic effect in enhancing expression of the reporter , but repressing its expression during murine infection. Taken together, the results demonstrate that the regulatory structure functions oppositely in the two different environments and potentially provides with a molecular mechanism to quickly adapt to the distinct environments during its enzootic life cycle.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.036608-0
2010-07-01
2020-01-21
Loading full text...

Full text loading...

/deliver/fulltext/micro/156/7/2194.html?itemId=/content/journal/micro/10.1099/mic.0.036608-0&mimeType=html&fmt=ahah

References

  1. Battisti, J. M., Bono, J. L., Rosa, P. A., Schrumpf, M. E., Schwan, T. G. & Policastro, P. F. ( 2008; ). Outer surface protein A protects Lyme disease spirochetes from acquired host immunity in the tick vector. Infect Immun 76, 5228–5237.[CrossRef]
    [Google Scholar]
  2. Bykowski, T., Babb, K., von Lackum, K., Riley, S. P., Norris, S. J. & Stevenson, B. ( 2006; ). Transcriptional regulation of the Borrelia burgdorferi antigenically variable VlsE surface protein. J Bacteriol 188, 4879–4889.[CrossRef]
    [Google Scholar]
  3. Caimano, M. J., Eggers, C. H., Gonzalez, C. A. & Radolf, J. D. ( 2005; ). Alternate sigma factor RpoS is required for the in vivo-specific repression of Borrelia burgdorferi plasmid lp54-borne ospA and lp6.6 genes. J Bacteriol 187, 7845–7852.[CrossRef]
    [Google Scholar]
  4. Caimano, M. J., Iyer, R., Eggers, C. H., Gonzalez, C., Morton, E. A., Gilbert, M. A., Schwartz, I. & Radolf, J. D. ( 2007; ). Analysis of the RpoS regulon in Borrelia burgdorferi in response to mammalian host signals provides insight into RpoS function during the enzootic cycle. Mol Microbiol 65, 1193–1217.[CrossRef]
    [Google Scholar]
  5. Collado-Vides, J., Magasanik, B. & Gralla, J. D. ( 1991; ). Control site location and transcriptional regulation in Escherichia coli. Microbiol Rev 55, 371–394.
    [Google Scholar]
  6. 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]
  7. 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]
  8. Eggers, C. H., Caimano, M. J. & Radolf, J. D. ( 2004; ). Analysis of promoter elements involved in the transcriptional initiation of RpoS-dependent Borrelia burgdorferi genes. J Bacteriol 186, 7390–7402.[CrossRef]
    [Google Scholar]
  9. 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]
  10. 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]
  11. He, M., Boardman, B. K., Yan, D. & Yang, X. F. ( 2007; ). Regulation of expression of the fibronectin-binding protein BBK32 in Borrelia burgdorferi. J Bacteriol 189, 8377–8380.[CrossRef]
    [Google Scholar]
  12. He, M., Oman, T., Xu, H., Blevins, J., Norgard, M. V. & Yang, X. F. ( 2008; ). Abrogation of ospAB constitutively activates the Rrp2-RpoN-RpoS pathway (σ N-σ S cascade) in Borrelia burgdorferi. Mol Microbiol 70, 1453–1464.[CrossRef]
    [Google Scholar]
  13. Hodzic, E., Tunev, S., Feng, S., Freet, K. J. & Barthold, S. W. ( 2005; ). Immunoglobulin-regulated expression of Borrelia burgdorferi outer surface protein A in vivo. Infect Immun 73, 3313–3321.[CrossRef]
    [Google Scholar]
  14. Howe, T. R., LaQuier, F. W. & Barbour, A. G. ( 1986; ). Organization of genes encoding two outer membrane proteins of the Lyme disease agent Borrelia burgdorferi within a single transcriptional unit. Infect Immun 54, 207–212.
    [Google Scholar]
  15. 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]
  16. Jonsson, M., Noppa, L., Barbour, A. G. & Bergstrom, S. ( 1992; ). Heterogeneity of outer membrane proteins in Borrelia burgdorferi: comparison of osp operons of three isolates of different geographic origins. Infect Immun 60, 1845–1853.
    [Google Scholar]
  17. Liang, F. T., Nelson, F. K. & Fikrig, E. ( 2002; ). Molecular adaptation of Borrelia burgdorferi in the murine host. J Exp Med 196, 275–280.[CrossRef]
    [Google Scholar]
  18. 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]
  19. 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]
  20. Lucchetti-Miganeh, C., Burrowes, E., Baysse, C. & Ermel, G. ( 2008; ). The post-transcriptional regulator CsrA plays a central role in the adaptation of bacterial pathogens to different stages of infection in animal hosts. Microbiology 154, 16–29.[CrossRef]
    [Google Scholar]
  21. Miller, J. C. & Stevenson, B. ( 2006; ). Borrelia burgdorferi erp genes are expressed at different levels within tissues of chronically infected mammalian hosts. Int J Med Microbiol 296 (Suppl. 40), 185–194.[CrossRef]
    [Google Scholar]
  22. 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]
  23. 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]
  24. Pal, U., Li, X., Wang, T., Montgomery, R. R., Ramamoorthi, N., Desilva, A. M., Bao, F., Yang, X., Pypaert, M. & other authors ( 2004a; ). TROSPA, an Ixodes scapularis receptor for Borrelia burgdorferi. Cell 119, 457–468.[CrossRef]
    [Google Scholar]
  25. Pal, U., Yang, X., Chen, M., Bockenstedt, L. K., Anderson, J. F., Flavell, R. A., Norgard, M. V. & Fikrig, E. ( 2004b; ). OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands. J Clin Invest 113, 220–230.[CrossRef]
    [Google Scholar]
  26. Purser, J. E. & Norris, S. J. ( 2000; ). Correlation between plasmid content and infectivity in Borrelia burgdorferi. Proc Natl Acad Sci U S A 97, 13865–13870.[CrossRef]
    [Google Scholar]
  27. 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]
  28. Sadziene, A., Thomas, D. D. & Barbour, A. G. ( 1995; ). Borrelia burgdorferi mutant lacking Osp: biological and immunological characterization. Infect Immun 63, 1573–1580.
    [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. Shi, Y., Xu, Q., McShan, K. & Liang, F. T. ( 2008; ). Both decorin-binding proteins A and B are critical for the overall virulence of Borrelia burgdorferi. Infect Immun 76, 1239–1246.[CrossRef]
    [Google Scholar]
  32. Sohaskey, C. D., Zuckert, W. R. & Barbour, A. G. ( 1999; ). The extended promoters for two outer membrane lipoprotein genes of Borrelia spp. uniquely include a T-rich region. Mol Microbiol 33, 41–51.[CrossRef]
    [Google Scholar]
  33. Stewart, P. E., Thalken, R., Bono, J. L. & Rosa, P. ( 2001; ). Isolation of a circular plasmid region sufficient for autonomous replication and transformation of infectious Borrelia burgdorferi. Mol Microbiol 39, 714–721.[CrossRef]
    [Google Scholar]
  34. 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]
  35. 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]
  36. 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]
  37. 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]
  38. 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]
  39. 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]
  40. 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]
  41. Xu, Q., McShan, K. & Liang, F. T. ( 2008a; ). Modification of Borrelia burgdorferi to overproduce OspA or VlsE alters its infectious behaviour. Microbiology 154, 3420–3429.[CrossRef]
    [Google Scholar]
  42. Xu, Q., McShan, K. & Liang, F. T. ( 2008b; ). Essential protective role attributed to the surface lipoproteins of Borrelia burgdorferi against innate defences. Mol Microbiol 69, 15–29.[CrossRef]
    [Google Scholar]
  43. 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]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.036608-0
Loading
/content/journal/micro/10.1099/mic.0.036608-0
Loading

Data & Media loading...

Supplements

vol. , part 7, pp. 2194 - 2204

Supplementary tables [ PDF, 95 kb]: Constructs and clones used in the study Primers used in the study



PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error