Rrp1, a cyclic-di-GMP-producing response regulator, is an important regulator of Borrelia burgdorferi core cellular functions

Molecular Microbiology

Volumn 71, Issue 6, 2009, Pages 1551-1573

  Rogers, Elizabeth A ^c   Terekhova, Darya ^a,c   Zhang, Hong Ming ^c   Hovis, Kelley M ^b,c   Schwartz, Ira ^c   Marconi, Richard T ^c,d  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF MARYLAND   (United States)

^c VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d NEW YORK MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL PROTEIN; CYCLIC DIGUANYLATE; CYCLIC GMP; PROTEIN BB0420; PROTEIN HISTIDINE KINASE; PROTEIN HPK1; PROTEIN RRP1; REGULATOR PROTEIN; UNCLASSIFIED DRUG;

ALLELE; ARTICLE; BORRELIA BURGDORFERI; GENE EXPRESSION REGULATION; IN VITRO STUDY; LYME DISEASE; NONHUMAN; OPEN READING FRAME; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DOMAIN; PROTEIN PHOSPHORYLATION; REGULON; SECOND MESSENGER; TWO COMPONENT SYSTEM;

AMINO ACID SEQUENCE; BACTERIAL PROTEINS; BORRELIA BURGDORFERI; CYCLIC GMP; GENE DELETION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, BACTERIAL; GENES, BACTERIAL; GENES, REGULATOR; MOLECULAR SEQUENCE DATA; MUTAGENESIS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; REGULON; RNA, BACTERIAL; SEQUENCE ALIGNMENT; SEQUENCE ANALYSIS, DNA;

BORRELIA; BORRELIA BURGDORFERI; IXODIDA;

EID: 62449269945     PISSN: 0950382X     EISSN: 13652958     Source Type: Journal    
DOI: 10.1111/j.1365-2958.2009.06621.x     Document Type: Article

References (109)

1. Alitalo, A., Meri, T., Chen, T., Lankinen, H., Cheng, Z.Z., Jokiranta, T.S., et al. (2004) Lysine-dependent multipoint binding of the Borrelia burgdorferi virulence factor outer surface protein E to the C terminus of factor H. J Immunol 172 : 6195 6201.
2. Amikam, D. Galperin, M.Y. (2006) PilZ domain is part of the bacterial c-di-GMP binding protein. Bioinformatics 22 : 3 6.
3. Anderson, J.F. Magnarelli, L.A. (2008) Biology of ticks. Infect Dis Clin North Am 22 : 195 215, v.
4. Antonara, S., Chafel, R.M., Lafrance, M. Coburn, J. (2007) Borrelia burgdorferi adhesins identified using in vivo phage display. Mol Microbiol 66 : 262 276.
5. Ausmees, N., Mayer, R., Weinhouse, H., Volman, G., Amikam, D., Benziman, M. Lindberg, M. (2001) Genetic data indicate that proteins containing the GGDEF domain possess diguanylate cyclase activity. FEMS Microbiol Lett 204 : 163 167.
6. Barbour, A.G., Jasinskas, A., Kayala, M.A., Davies, D.H., Steere, A.C., Baldi, P. Felgner, P.L. (2008) A genome-wide proteome array reveals a limited set of immunogens in natural infections of humans and white-footed mice with Borrelia burgdorferi. Infect Immun 76 : 3374 3389.
7. Benach, J.L., Bosler, E.M., Hanrahan, J.P., Coleman, J.L., Bast, T.F., Habicht, G.S., et al. (1983) Spirochetes isolated from the blood of two patients with Lyme disease. N Engl J Med 308 : 740 742.
8. Benach, J., Swaminathan, S.S., Tamayo, R., Handelman, S.K., Folta-Stogniew, E., Ramos, J.E., et al. (2007) The structural basis of cyclic diguanylate signal transduction by PilZ domains. EMBO J 26 : 5153 5166.
9. Beyhan, S., Tischler, A.D., Camilli, A. Yildiz, F.H. (2006) Transcriptome and phenotypic responses of Vibrio cholerae to increased cyclic di-GMP level. J Bacteriol 188 : 3600 3613.
10. Boardman, B.K., He, M., Ouyang, Z., Xu, H., Pang, X. Yang, X.F. (2008) Essential role of the response regulator Rrp2 in the infectious cycle of Borrelia burgdorferi. Infect Immun 76 : 3844 3853.
11. Bobrov, A.G., Kirillina, O. Perry, R.D. (2007) Regulation of biofilm formation in Yersinia pestis. Adv Exp Med Biol 603 : 201 210.
12. Brooks, C.S., Hefty, P.S., Joliff, S.E. Akins, D.R. (2003) Global analysis of Borrelia burgdorferi genes regulated by mammalian host-specific signals. Infect Immun 71 : 3371 3383.
13. Brooks, C.S., Vuppala, S.R., Jett, A.M., Alitalo, A., Meri, S. Akins, D.R. (2005) Complement regulator-acquiring surface protein 1 imparts resistance to human serum in Borrelia burgdorferi. J Immunol 175 : 3299 3308.
14. Brown, E.L., Guo, B.P., O'Neal, P. Hook, M. (1999) Adherence of Borrelia burgdorferi. Identification of critical lysine residues in DbpA required for decorin binding. J Biol Chem 274 : 26272 26278.
15. Brussow, H., Canchaya, C. Hardt, W.-D. (2004) Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol Mol Biol Rev 68 : 560 602.
16. Burgdorfer, W., Barbour, A.G., Hayes, S.F., Benach, J.L., Grunwaldt, E. Davis, J.P. (1982) Lyme disease - a tick-borne spirochetosis? Science 216 : 1317 1319.
17. Burtnick, M.N., Downey, J.S., Brett, P.J., Boylan, J.A., Frye, J.G., Hoover, T.R. Gherardini, F.C. (2007) Insights into the complex regulation of rpoS in Borrelia burgdorferi. Mol Microbiol 65 : 277 293.
18. Caimano, M.J., Iyer, R., Eggers, C.H., Gonzalez, C., Morton, E.A., Gilbert, M.A., et al. (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.
19. Canchaya, C., Fournous, G. Brussow, H. (2004) The impact of prophages on bacterial chromosomes. Mol Microbiol 53 : 9 18.
20. Carlyon, J.A., Roberts, D.M. Marconi, R.T. (2000a) Evolutionary and molecular analyses of the Borrelia bdr super gene family: delineation of distinct sub-families and demonstration of the genus wide conservation of putative functional domains, structural properties and repeat motifs. Microb Pathog 28 : 89 105.
21. Carlyon, J.A., Roberts, D.M., Theisen, M., Sadler, C. Marconi, R.T. (2000b) Molecular and immunological analyses of the Borrelia turicatae Bdr protein family. Infect Immun 68 : 2369 2373.
22. Carroll, J.A., Cordova, R.M. Garon, C.F. (2000) Identification of 11 pH-regulated genes in Borrelia burgdorferi localizing to linear plasmids. Infection Immunity 68 : 6677 6684.
23. Casjens, S. (2003) Prophage and bacterial genomics: what have we learned so far? Mol Microbiol 49 : 277 300.
24. Casjens, S., Palmer, N., van Vugt, R., Huang, W.M., Stevenson, B., Rosa, P., et al. (2000) A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi. Mol Microbiol 35 : 490 516.
25. Cotter, P.A. Stibitz, S. (2007) c-di-GMP-mediated regulation of virulence and biofilm formation. Curr Opin Microbiol 10 : 17 23.
26. Cunningham, T.M., Walker, E.M., Miller, J.N. Lovett, M.A. (1988) Selective release of the Treponema pallidum outer membrane and associated polypeptides with Triton X-114. J Bacteriol 170 : 387 395.
27. Eggers, C. Samuels, D.S. (1999) Molecular evidence for a new bacteriophage of Borrelia burgdorferi. J Bacteriol 181 : 7308 7313.
28. Eggers, C.H., Casjens, S., Hayes, S.F., Garon, C.F., Damman, C.J., Oliver, D.B. Samuels, D.S. (2000) Bacteriophages of spirochetes. J Mol Microbiol Biotechnol 4 : 365 373.
29. Eggers, C.H., Kimmel, B.J., Bono, J.L., Elias, A.F., Rosa, P. Samuels, D.S. (2001) Transduction by phiBB-1, a bacteriophage of Borrelia burgdorferi. J Bacteriol 183 : 4771 4778.
30. 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.
31. Eggers, C.H., Caimano, M.J. Radolf, J.D. (2006) Sigma factor selectivity in Borrelia burgdorferi: RpoS recognition of the ospE/ospF/elp promoters is dependent on the sequence of the -10 region. Mol Microbiol 59 : 1859 1875.
32. 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 4543.
33. Embers, M.E., Alvarez, X., Ooms, T. Philipp, M.T. (2008) The failure of immune response evasion by linear plasmid 28-1-deficient Borrelia burgdorferi is attributable to persistent expression of an outer surface protein. Infect Immun 76 : 3984 3991.
34. Fisher, M.A., Grimm, D., Henion, A.K., Elias, A.F., Stewart, P.E., Rosa, P.A. Gherardini, F.C. (2005) From the cover: Borrelia burgdorferi {sigma}54 is required for mammalian infection and vector transmission but not for tick colonization. Proc Natl Acad Sci USA 102 : 5162 5167.
35. Frank, K.L., Bundle, S.F., Kresge, M.E., Eggers, C.H. Samuels, D.S. (2003) aadA confers streptomycin resistance in Borrelia burgdorferi. J Bacteriol 185 : 6723 6727.
36. Fraser, C., Casjens, S., Huang, W.M., Sutton, G.G., Clayton, R., Lathigra, R., et al. (1997) Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390 : 580 586.
37. Galperin, M.Y. (2006) Structural classification of bacterial response regulators: diversity of output domains and domain combinations. J Bacteriol 188 : 4169 4182.
38. Galperin, M.Y., Nikolskaya, A.N. Koonin, E.V. (2001) Novel domains of the prokaryotic two-component signal transduction systems. FEMS Microbiol Lett 203 : 11 21.
39. Garcia, B., Latasa, C., Solano, C., Garcia-del Portillo, F., Gamazo, C. Lasa, I. (2004) Role of the GGDEF protein family in Salmonella cellulose biosynthesis and biofilm formation. Mol Microbiol 54 : 264 277.
40. Gjermansen, M., Ragas, P. Tolker-Nielsen, T. (2006) Proteins with GGDEF and EAL domains regulate Pseudomonas putida biofilm formation and dispersal. FEMS Microbiol Lett 265 : 215 224.
41. Guvener, Z.T. Harwood, C.S. (2007) Subcellular location characteristics of the Pseudomonas aeruginosa GGDEF protein, WspR, indicate that it produces cyclic-di-GMP in response to growth on surfaces. Mol Microbiol 66 : 1459 1473.
42. 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.
43. Hefty, P.S., Jolliff, S.E., Caimano, M.J., Wikel, S.K., Radolf, J.D. Akins, D.R. (2001) Regulation of the OspE-related, OspF-related, and Elp lipoproteins of Borrelia burgdorferi strain 297 by mammalian host-specific signals. Infect Immun 69 : 3618 3627.
44. Hefty, P.S., Brooks, C.S., Jett, A.M., White, G.L., Wikel, S.K., Kennedy, R.C. Akins, D.R. (2002) OspE-related, OspF-related and Elp lipoproteins are immunogenic in baboons experimentally infected with Borrelia burgdorferi and in human Lyme disease patients. J Clin Microbiol 40 : 4256 4265.
45. Hellwage, J., Meri, T., Heikkila, T., Alitalo, A., Panelius, J., Lahdenne, P., et al. (2001) The complement regulator factor H binds to the surface protein OspE of Borrelia burgdorferi. J Biol Chem 276 : 8427 8435.
46. Hovis, K.M., Jones, J.P., Sadlon, T., Raval, G., Gordon, D.L. Marconi, R.T. (2006a) Molecular analyses of the interaction of Borrelia hermsii FhbA with the complement regulatory proteins factor H and factor H-like protein 1. Infect Immun 74 : 2007 2014.
47. Hovis, K.M., Tran, E., Sundy, C.M., Buckles, E., McDowell, J.V. Marconi, R.T. (2006b) Selective binding of Borrelia burgdorferi OspE paralogs to factor H and serum proteins from diverse animals: possible expansion of the role of OspE in Lyme disease pathogenesis. Infect Immun 74 : 1967 1972.
48. 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 USA 98 : 12724 12729.
49. Hyde, J.A., Seshu, J. Skare, J.T. (2006) Transcriptional profiling of Borrelia burgdorferi containing a unique bosR allele identifies a putative oxidative stress regulon. Microbiology 152 : 2599 2609.
50. 2 levels. J Bacteriol 189 : 437 445.
51. Iyer, R., Kalu, O., Purser, J., Norris, S., Stevenson, B. Schwartz, I. (2003) Linear and circular plasmid content in Borrelia burgdorferi clinical isolates. Infect Immun 71 : 3699 3706.
52. Jenal, U. Malone, J. (2006) Mechanisms of cyclic-di-GMP signaling in bacteria. Annu Rev Genet 40 : 385 407.
53. Karaolis, D.K., Rashid, M.H., Chythanya, R., Luo, W., Hyodo, M. Hayakawa, Y. (2005) c-di-GMP (3′-5′-cyclic diguanylic acid) inhibits Staphylococcus aureus cell-cell interactions and biofilm formation. Antimicrob Agents Chemother 49 : 1029 1038.
54. Kim, Y.K. McCarter, L.L. (2007) ScrG, a GGDEF-EAL protein, participates in regulating swarming and sticking in Vibrio parahaemolyticus. J Bacteriol 189 : 4094 4107.
55. Kraiczy, P. Würzner, R. (2005) Complement escape of human pathogenic bacteria by acquisition of complement regulators. Mol Immunol 43 : 31 44.
56. Kraiczy, P., Hellwage, J., Skerka, C., Becker, H., Kirschfink, M., Simon, M.S., 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 Biolog Chem 279 : 2421 2429.
57. Lam, T.T., Nguyen, T.P., Montgomery, R.R., Kantor, F.S., Fikrig, E. Flavell, R.A. (1994) Outer surface proteins E and F of Borrelia burgdorferi, the agent of Lyme disease. Infect Immun 62 : 290 298.
58. Lawrenz, M.B., Kawabata, H., Purser, J.E. Norris, S.J. (2002) Decreased electroporation efficiency in Borrelia burgdorferi containing lineaer plasmids lp25 and lp56: Impact on transformation of infectious B. burgdorferi. Infect Immun 70 : 4798 4804.
59. Lee, V.T., Matewish, J.M., Kessler, J.L., Hyodo, M., Hayakawa, Y. Lory, S. (2007) A cyclic-di-GMP receptor required for bacterial exopolysaccharide production. Mol Microbiol 65 : 1474 1484.
60. Lescot, M., Audic, S., Robert, C., Nguyen, T.T., Blanc, G., Cutler, S.J., et al. (2008) The genome of Borrelia recurrentis, the agent of deadly louse-borne relapsing fever, is a degraded subset of tick-borne Borrelia duttonii. PLoS Genet 4 : e1000185.
61. Lybecker, M.C. Samuels, D.S. (2007) Temperature-induced regulation of RpoS by a small RNA in Borrelia burgdorferi. Mol Microbiol 64 : 1075 1089.
62. McDowell, J.V., Sung, S.Y., Labandeira-Rey, M., Skare, J.T. Marconi, R.T. (2001) Analysis of mechanisms associated with loss of infectivity of clonal populations of Borrelia burgdorferi B31MI. Infect Immun 69 : 3670 3677.
63. McDowell, J.V., Wolfgang, J., Tran, E., Metts, M.S., Hamilton, D. Marconi, R.T. (2003) Comprehensive analysis of the factor H binding capabilities of Borrelia species associated with Lyme disease: delineation of two distinct classes of factor H binding proteins. Infect Immun 71 : 3597 3602.
64. McDowell, J.V., Wolfgang, J., Senty, L., Sundy, C.M., Noto, M.J. Marconi, R.T. (2004) Demonstration of the involvement of outer surface protein E coiled coil structural domains and higher order structural elements in the binding of infection-induced antibody and the complement-regulatory protein, factor H. J Immunol 173 : 7471 7480.
65. Meissner, A., Wild, V., Simm, R., Rohde, M., Erck, C., Bredenbruch, F., et al. (2007) Pseudomonas aeruginosa cupA-encoded fimbriae expression is regulated by a GGDEF and EAL domain-dependent modulation of the intracellular level of cyclic diguanylate. Environ Microbiol 9 : 2475 2485.
66. Mendez-Ortiz, M.M., Hyodo, M., Hayakawa, Y. Membrillo-Hernandez, J. (2006) Genome wide transcriptional profile of Escherichia coli in response to high levels of the second messenger c-di-GMP. J Biol Chem 281 : 8090 8099.
67. Narasimhan, S., Santiago, F., Koski, R.A., Brei, B., Anderson, J.F., Fish, D. Fikrig, E. (2002) Examination of the Borrelia burgdorferi transcriptome in Ixodes scapularis during feeding. J Bacteriol 184 : 3122 3125.
68. Ojaimi, C., Brooks, C., Casjens, S., Rosa, P., Elias, A., Barbour, A.G., et al. (2003) Profiling of temperature-induced changes in Borrelia burgdorferi gene expression by using whole genome arrays. Infect Immun 71 : 1689 1705.
69. Ojaimi, C., Mulay, V., Liveris, D., Iyer, R. Schwartz, I. (2005) Comparative transcriptional profiling of Borrelia burgdorferi clinical isolates differing in capacities for hematogenous dissemination. Infect Immun 73 : 6791 6802.
70. Ouyang, Z., Blevins, J.S. Norgard, M.V. (2008) Transcriptional interplay among the regulators Rrp2, RpoN and RpoS in Borrelia burgdorferi. Microbiology 154 : 2641 2658.
71. Palmer, N., Fraser, C. Casjens, S. (2000) Distribution of twelve linear extrachromosomal DNAs in natural isolates of Lyme disease spirochetes. J Bacteriol 182 : 2476 2480.
72. Pikas, D.S., Brown, E.L., Gurusiddappa, S., Lee, L.Y., Xu, Y. Hook, M. (2003) Decorin-binding sites in the adhesin DbpA from Borrelia burgdorferi: a synthetic peptide approach. J Biol Chem 278 : 30920 30926.
73. Porcella, S.F., Fitzpatrick, C.A. Bono, J.L. (2000) Expression and immunological analysis of the plasmid-borne mlp genes of Borrelia burgdorferi strain B31. Infect Immun 68 : 4992 5001.
74. Purser, J.E. Norris, S.J. (2000) Correlation between plasmid content and infectivity in Borrelia burgdorferi. Proc Natl Acad Sci USA 97 : 13865 13870.
75. 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.
76. Revel, A.T., Talaat, A.M. Norgard, M.V. (2002) DNA microarray analysis of differential gene expression in Borrelia burgdorferi, the Lyme disease spirochete. Proc Natl Acad Sci USA 99 : 1562 1567.
77. Roberts, D.M., Carlyon, J.A., Theisen, M. Marconi, R.T. (2000) The bdr gene families of the Lyme disease and relapsing fever spirochetes: potential influence on biology, pathogenesis, and evolution. Emerg Infect Dis 6 : 110 122.
78. Roberts, D.M., Caimano, M., McDowell, J., Theisen, M., Holm, A., Orff, E., et al. (2002) Environmental regulation and differential production of members of the Bdr protein family of Borrelia burgdorferi. Infect Immun 70 : 7033 7041.
79. Rogers, E.A. Marconi, R.T. (2007) Delineation of species-specific binding properties of the CspZ protein (BBH06) of Lyme disease spirochetes: evidence for new contributions to the pathogenesis of Borrelia spp. Infect Immun 75 : 5272 5281.
80. Romling, U. Amikam, D. (2006) Cyclic di-GMP as a second messenger. Curr Opin Microbiol 9 : 218 228.
81. Romling, U., Gomelsky, M. Galperin, M.Y. (2005) C-di-GMP: the dawning of a novel bacterial signalling system. Mol Microbiol 57 : 629 639.
82. Ryjenkov, D.A., Tarutina, M., Moskvin, O.V. Gomelsky, M. (2005) Cyclic diguanylate is a ubiquitous signaling molecule in bacteria: insights into biochemistry of the GGDEF protein domain. J Bacteriol 187 : 1792 1798.
83. Ryjenkov, D.A., Simm, R., Romling, U. Gomelsky, M. (2006) The PilZ domain is a receptor for the second messenger c-di-GMP: the PilZ domain protein YcgR controls motility in enterobacteria. J Biol Chem 281 : 30310 30314.
84. Samuels, D.S., Mach, K. Garon, C.F. (1994) Genetic transformation of the Lyme disease agent Borrelia burgdorferi with coumarin-resistant gyrB. J Bacteriol 176 : 6045 6049.
85. Seshu, J., Boylan, J.A., Gherardini, F.C. Skare, J.T. (2004) Dissolved oxygen levels alter gene expression and antigen profiles in Borrelia burgdorferi. Infect Immun 72 : 1580 1586.
86. Shih, C.M., Chao, L.L. Yu, C.P. (2002) Chemotactic migration of the Lyme disease spirochete (Borrelia burgdorferi) to salivary gland extracts of vector ticks. Am J Trop Med Hyg 66 : 616 621.
87. Shu, C.J. Zhulin, I.B. (2002) ANTAR: an RNA-binding domain in transcription antitermination regulatory proteins. Trends Biochem Sci 27 : 3 5.
88. Simm, R., Morr, M., Kader, A., Nimtz, M. Romling, U. (2004) GGDEF and EAL domains inversely regulate cyclic di-GMP levels and transition from sessility to motility. Mol Microbiol 53 : 1123 1134.
89. Simm, R., Fetherston, J.D., Kader, A., Romling, U. Perry, R.D. (2005) Phenotypic convergence mediated by GGDEF-domain-containing proteins. J Bacteriol 187 : 6816 6823.
90. Skerker, J.M., Perchuk, B.S., Siryaporn, A., Lubin, E.A., Ashenberg, O., Goulian, M. Laub, M.T. (2008) Rewiring the specificity of two-component signal transduction systems. Cell 133 : 1043 1054.
91. Steere, A.C., Grodzicki, R.L., Kornblatt, A.N., Craft, J.E., Barbour, A.G., Burgdorfer, W., et al. (1983) The spirochetal etiology of Lyme disease. N Engl J Med 308 : 733 740.
92. Stewart, P.E., Byram, R., Grimm, D., Tilly, K. Rosa, P.A. (2005) The plasmids of Borrelia burgdorferi: essential genetic elements of a pathogen. Plasmid 53 : 1 13.
93. Stock, A.M., Robinson, V.L. Goudreau, P.N. (2000) Two-component signal transduction. Annu Rev Biochem 69 : 183 215.
94. Sudarsan, N., Lee, E.R., Weinberg, Z., Moy, R.H., Kim, J.N., Link, K.H. Breaker, R.R. (2008) Riboswitches in eubacteria sense the second messenger cyclic di-GMP. Science 321 : 411 413.
95. Tamayo, R., Pratt, J.T. Camilli, A. (2007) Roles of cyclic diguanylate in the regulation of bacterial pathogenesis. Annu Rev Microbiol 61 : 131 148.
96. Terekhova, D., Iyer, R., Wormser, G.P. Schwartz, I. (2006) Comparative genome hybridization reveals substantial variation among clinical isolates of Borrelia burgdorferi sensu stricto with different pathogenic properties. J Bacteriol 188 : 6124 6134.
97. Tischler, A.D. Camilli, A. (2004) Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation. Mol Microbiol 53 : 857 869.
98. Tokarz, R., Anderton, J., Katona, L. Benach, J. (2004) Combined effects of blood and temperature shift on Borrelia burgdorferi gene expression as determined by whole genome DNA array. Infect Immun 72 : 5419 5432.
99. Weinberg, Z., Barrick, J.E., Yao, Z., Roth, A., Kim, J.N., Gore, J., et al. (2007) Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline. Nucleic Acids Res 35 : 4809 4819.
100. West, A.H. Stock, A.M. (2001) Histidine kinases and response regulator proteins in two-component signaling systems. Trends Biochem Sci 26 : 369 376.
101. Wolfe, A.J. Visick, K.L. (2008) Get the message out: cyclic-di-GMP regulates multiple levels of flagellum-based motility. J Bacteriol 190 : 463 475.
102. Xu, Y., Kodner, C., Coleman, L. Johnson, R.C. (1996) Correlation of plasmids with infectivity of Borrelia burgdorferi sensu stricto type strain B31. Infect Immun 64 : 3870 3876.
103. Xu, Y., Bruno, J.F. Luft, B.J. (2003) Detection of genetic diversity in linear plasmids 28-3 and 36 in Borrelia burgdorferi sensu stricto isolates by subtractive hybridization. Microb Pathog 35 : 269 278.
104. Yang, X., Popova, T.G., Hagman, K.E., Wikel, S.K., Schoeler, G.B., Caimano, M.J., 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 6018.
105. Yang, X.F., Alani, S.M. Norgard, M.V. (2003a) The response regulator Rrp2 is essential for the expression of major membrane lipoproteins in Borrelia burgdorferi. Proc Natl Acad Sci USA 100 : 11001 11006.
106. Yang, X.F., Hubner, A., Popova, T.G., Hagman, K.E. Norgard, M.V. (2003b) Regulation of expression of the paralogous Mlp family in Borrelia burgdorferi. Infect Immun 71 : 5012 5020.
107. Zhang, H. Marconi, R.T. (2005) Demonstration of cotranscription and 1-methyl-3-nitroso-nitroguanidine induction of a 30-gene operon of Borrelia burgdorferi: evidence that the 32-kilobase circular plasmids are prophages. J Bacteriol 187 : 7985 7995.
108. Zhang, H., Raji, A., Theisen, M., Hansen, P.R. Marconi, R.T. (2005) bdrF2 of Lyme disease spirochetes is coexpressed with a series of cytoplasmic proteins and is produced specifically during early infection. J Bacteriol 187 : 175 184.
109. Zuckert, W.R., Meyer, J. Barbour, A.G. (1999) Comparative analysis and immunological characterization of the Borrelia Bdr protein family. Infect Immun 67 : 3257 3266.