The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi

Frontiers in Cellular and Infection Microbiology

Volumn 4, Issue MAY, 2014, Pages

  Novak, Elizabeth A ^a   Sultan, Syed Z ^a   Motaleb, Md A ^a  

^a EAST CAROLINA UNIVERSITY   (United States)

Author keywords

Borrelia burgdorferi; c di GMP; Chemotaxis; Lyme disease; Motility; Virulence

Indexed keywords

CYCLIC AMP; CYCLIC DIGUANYLATE; GUANOSINE PHOSPHATE; UNCLASSIFIED DRUG; BACTERIAL PROTEIN; BIS(3',5')-CYCLIC DIGUANYLIC ACID; CARRIER PROTEIN; CYCLIC GMP; CYCLIC GMP PHOSPHODIESTERASE; DIGUANYLATE CYCLASE; ESCHERICHIA COLI PROTEIN; LYASE; PROTEIN BINDING;

BACTERIAL VIRULENCE; BACTERIUM IDENTIFICATION; BORRELIA BURGDORFERI; CHEMOTAXIS; DISEASE TRANSMISSION; ENVIRONMENTAL CHANGE; ENZYME ACTIVITY; GENE EXPRESSION; GENETIC ANALYSIS; LYME DISEASE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PHENOTYPE; PROTEIN MOTIF; REVIEW; SIGNAL TRANSDUCTION; ANALOGS AND DERIVATIVES; ANIMAL; HUMAN; METABOLISM; MICROBIOLOGY; PHYSIOLOGY;

3',5'-CYCLIC-GMP PHOSPHODIESTERASES; ANIMALS; BACTERIAL PROTEINS; BORRELIA BURGDORFERI; CARRIER PROTEINS; CYCLIC GMP; ESCHERICHIA COLI PROTEINS; HUMANS; LYME DISEASE; PHOSPHORUS-OXYGEN LYASES; PROTEIN BINDING; SIGNAL TRANSDUCTION;

EID: 84923271143     PISSN: None     EISSN: 22352988     Source Type: Journal    
DOI: 10.3389/fcimb.2014.00056     Document Type: Review

References (160)

1. Adams, D. A., Gallagher, K. M., Jajosky, R. A., Kriseman, J., Sharp, P., Anderson, W. J., et al. (2013). Summary of notifiable diseases-United States, 2011. MMWR Morb. Mortal. Wkly. Rep. 60, 1-117.
2. Adams, D. A., Gallagher, K. M., Jajosky, R. A., Ward, J., Sharp, P., Anderson, W. J., et al. (2012). Summary of notifiable diseases-United States, 2010. MMWR Morb. Mortal. Wkly. Rep. 59, 1-111.
3. Albright, L. M., Huala, E., and Ausubel, F. M. (1989). Prokaryotic signal transduction mediated by sensor and regulator protein pairs. Annu. Rev. Genet. 23, 311-336. doi: 10.1146/annurev.ge.23.120189.001523
4. Amikam, D., and Galperin, M. Y. (2006). PilZ domain is part of the bacterial c-di-GMP binding protein. Bioinformatics 22, 3-6. doi: 10.1093/bioinformatics/bti739
5. Andrade, M. O., Alegria, M. C., Guzzo, C. R., Docena, C., Rosa, M. C., Ramos, C. H., et al. (2006). The HD-GYP domain of RpfG mediates a direct linkage between the Rpf quorum-sensing pathway and a subset of diguanylate cyclase proteins in the phytopathogen Xanthomonas axonopodis pv. citri. Mol. Microbiol. 62, 537-551. doi: 10.1111/j.1365-2958.2006.05386.x
6. Armitage, J. P., and Berry, R. M. (2010). Time for bacteria to slow down. Cell 141, 24-26. doi: 10.1016/j.cell.2010.03.023
7. Barends, T. R., Hartmann, E., Griese, J. J., Beitlich, T., Kirienko, N. V., Ryjenkov, D. A., et al. (2009). Structure and mechanism of a bacterial light-regulated cyclic nucleotide phosphodiesterase. Nature 459, 1015-1018. doi: 10.1038/nature07966
8. Barrett, P. N., and Portsmouth, D. (2013). The need for a new vaccine against Lyme borreliosis. Expert Rev. Vaccines 12, 101-103. doi: 10.1586/erv.12.141
9. Beier, D., and Gross, R. (2006). Regulation of bacterial virulence by two-component systems. Curr. Opin. Microbiol. 9, 143-152. doi: 10.1016/j.mib.2006.01.005
10. 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. doi: 10.1038/sj.emboj.7601918
11. Berg, H. C. (2003). The rotary motor of bacterial flagella. Annu. Rev. Biochem. 72, 19-54. doi: 10.1146/annurev.biochem.72.121801.161737
12. Bian, J., Liu, X., Cheng, Y. Q., and Li, C. (2013). Inactivation of cyclic Di-GMP binding protein TDE0214 affects the motility, biofilm formation, and virulence of Treponema denticola. J. Bacteriol. 195, 3897-3905. doi: 10.1128/JB.00610-13
13. Blevins, J. S., Xu, H., He, M., Norgard, M. V., Reitzer, L., and Yang, X. F. (2009). Rrp2, a s54-dependent trasncriptional activator of Borrelia burgdorferi, activates rpoS in an enhancer-independent manner. J. Bacteriol. 191, 2902-2905. doi: 10.1128/JB.01721-08
14. Boardman, B. K., He, M., Ouyang, Z., Xu, H., Pang, X., and Yang, X. F. (2008). Essential role of the response regulator Rrp2 in the infectious cycle of Borrelia burgdorferi. Infect. Immun. 76, 3844-3853. doi: 10.1128/IAI.00467-08
15. Bobrov, A. G., Kirillina, O., Forman, S., Mack, D., and Perry, R. D. (2008). Insights into Yersinia pestis biofilm development: topology and co-interaction of Hms inner membrane proteins involved in exopolysaccharide production. Environ. Microbiol. 10, 1419-1432. doi: 10.1111/j.1462-2920.2007.01554.x
16. Boehm, A., Kaiser, M., Li, H., Spangler, C., Kasper, C. A., Ackermann, M., et al. (2010). Second messenger-mediated adjustment of bacterial swimming velocity. Cell 141, 107-116. doi: 10.1016/j.cell.2010.01.018
17. Boylan, J. A., Posey, J. E., and Gherardini, F. C. (2003). Borrelia oxidative stress response regulator, BosR: a distinctive Zn-dependent transcriptional activator. Proc. Natl. Acad. Sci. U.S.A. 100, 11684-11689. doi: 10.1073/pnas.2032956100
18. Brisson, D., Drecktrah, D., Eggers, C. H., and Samuels, D. S. (2012). Genetics of Borrelia burgdorferi. Annu. Rev. Genet. 46, 515-536. doi: 10.1146/annurev-genet-011112-112140
19. Brooks, C. S., Hefty, P. S., Jolliff, S. E., and Akins, D. R. (2003). Global analysis of Borrelia burgdorferi genes regulated by mammalian host-specific signals. Infect. Immun. 71, 3371-3383. doi: 10.1128/IAI.71.6.3371-3383.2003
20. Brown, N. L., Misra, T. K., Winnie, J. N., Schmidt, A., Seiff, M., and Silver, S. (1986). The nucleotide sequence of the mercuric resistance operons of plasmid R100 and transposon Tn501: further evidence for mer genes which enhance the activity of the mercuric ion detoxification system. Mol. Gen. Genet. 202, 143-151. doi: 10.1007/BF00330531
21. Burgdorfer, W., Barbour, A. G., Hayes, S. F., Benach, J. L., Grunwaldt, E., and Davis, J. P. (1982). Lyme disease-a tick-borne spirochetosis? Science 216, 1317-1319. doi: 10.1126/science.7043737
22. Burtnick, M. N., Downey, J. S., Brett, P. J., Boylan, J. A., Frye, J. G., Hoover, T. R., et al. (2007). Insights into the complex regulation of rpoS in Borrelia burgdorferi. Mol. Microbiol. 65, 277-293. doi: 10.1111/j.1365-2958.2007.05813.x
23. Caimano, M. J., Eggers, C. H., Hazlett, K. R., and Radolf, J. D. (2004). RpoS is not central to the general stress response in Borrelia burgdorferi but does control expression of one or more essential virulent determinants. Infect. Immun. 72, 6433-6445. doi: 10.1128/IAI.72.11.6433-6445.2004
24. 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. doi: 10.1111/j.1365-2958.2007.05860.x
25. Caimano, M. J., Kenedy, M. R., Kairu, T., Desrosiers, D. C., Harman, M., Dunham-Ems, S., et al. (2011). The hybrid histidine kinase Hk1 is part of a two-component system that is essential for survival of Borrelia burgdorferi in feeding Ixodes scapularis ticks. Infect. Immun. 79, 3117-3130. doi: 10.1128/IAI.05136-11
26. Carroll, J. A., El-Hage, N., Miller, J. C., Babb, K., and Stevenson, B. (2001). Borrelia burgdorferi RevA antigen is a surface-exposed outer membrane protein whose expression is regulated in response to environmental temperature and pH. Infect. Immun. 69, 5286-5293. doi: 10.1128/IAI.69.9.5286-5293.2001
27. Carroll, J. A., Garcon, C. F., and Schwan, T. G. (1999). Effects of environmental pH on membrane proteins in Borrelia burgdorferi. Infect. Immun. 67, 3181-3187.
28. 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. doi: 10.1046/j.1365-2958.2000.01698.x
29. Chae, K. S., and Yoo, O. J. (1986). Cloning of the lambda resistant genes from Brevibacterium albidum and Proteus vulgaris into Escherichia coli. Biochem. Biophys. Res. Commun. 140, 1101-1105. doi: 10.1016/0006-291X(86)90748-5
30. Chang, A. L., Tuckerman, J. R., Gonzalez, G., Mayer, R., Weinhouse, H., Volman, G., et al. (2001). Phosphodiesterase A1, a regulator of cellulose synthesis in Acetobacter xylinum, is a heme-based sensor. Biochemistry 40, 3420-3426. doi: 10.1021/bi0100236
31. Chang, C., Jin, X., and Chaoqun, H. (2009). Phenotypic and genetic differences between opaque and translucent colonies of Vibrio alginolyticus. Biofouling 25, 525-531. doi: 10.1080/08927010902964578
32. Charon, N. W., Cockburn, A., Li, C., Liu, J., Miller, K. A., Miller, M. R., et al. (2012). The unique paradigm of spirochete motility and chemotaxis. Annu. Rev. Microbiol. 66, 349-370. doi: 10.1146/annurev-micro-092611-150145
33. Chatterjee, S., Wistrom, C., and Lindow, S. E. (2008). A cell-cell signaling sensor is required for virulence and insect transmission of Xylella fastidiosa. Proc. Natl. Acad. Sci. U.S.A. 105, 2670-2675. doi: 10.1073/pnas.0712236105
34. Christen, M., Christen, B., Allan, M. G., Folcher, M., Jenö, P., Grzesiek, S., et al. (2007). DgrA is a member of a new family of cyclic diguanosine monophosphate receptors and controls flagellar motor function in Caulobacter crescentus. Proc. Natl. Acad. Sci. U.S.A. 104, 4112-4117. doi: 10.1073/pnas.0607738104
35. Christen, M., Christen, B., Folcher, M., Schauerte, A., and Jenal, U. (2005). Identification and characterization of a cyclic di-GMP phosphodiesterase and its allosteric control by GTP. J. Biol. Chem. 280, 30829-30837. doi: 10.1074/jbc.M504429200
36. Christen, M., Kulasekara, H. D., Christen, B., Kulasekara, B. R., Hoffman, L. R., and Miller, S. I. (2010). Asymmetrical distribution of the second messenger c-di-GMP upon bacterial cell division. Science 328, 1295-1297. doi: 10.1126/science.1188658
37. Cotter, P. A., and Stibitz, S. (2007). c-di-GMP-mediated regulation of virulence and biofilm formation. Curr. Opin. Microbiol. 10, 17-23. doi: 10.1016/j.mib.2006.12.006
38. Duerig, A., Abel, S., Folcher, M., Nicollier, M., Schwede, T., Amiot, N., et al. (2009). Second messenger-mediated spatiotemporal control of protein degradation regulates bacterial cell cycle progression. Genes Dev. 23, 93-104. doi: 10.1101/gad.502409
39. Dunham-Ems, S. M., Caimano, M. J., Eggers, C. H., and Radolf, J. D. (2012). Borrelia burgdorferi requires the alternative sigma factor RpoS for dissemination within the vector during tick-to-mammal transmission. PLoS Pathog. 8:e1002532. doi: 10.1371/journal.ppat.1002532
40. Fang, X., and Gomelsky, M. (2010). A post-translational, c-di-GMP-dependent mechanism regulating flagellar motility. Mol. Microbiol. 76, 1295-1305. doi: 10.1111/j.1365-2958.2010.07179.x
41. Fazli, M., O'Connell, A., Nilsson, M., Niehaus, K., Dow, J. M., Givskov, M., et al. (2011). The CRP/FNR family protein Bcam1349 is a c-di-GMP effector that regulates biofilm formation in the respiratory pathogen Burkholderia cenocepacia. Mol. Microbiol. 82, 327-341. doi: 10.1111/j.1365-2958.2011.07814.x
42. Fisher, M. A., Grimm, D., Henion, A. K., Elias, A. F., Stewart, P. E., Rosa, P. A., et al. (2005). Borrelia burgdorferi s54 is required for mammalian infection and vector transmissionbut not for tick colonization. Proc. Natl. Acad. Sci. U.S.A. 102, 5162-5167. doi: 10.1073/pnas.0408536102
43. Fraser, C. M., 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. doi: 10.1038/37551
44. Freedman, J. C., Rogers, E. A., Kostick, J. L., Zhang, H., Iyer, R., Schwartz, I., et al. (2010). Identification and molecular characterization of a c-di-GMP effector protein, PlzA (BB0733): additional evidence for the existence of a functional c-di-GMP regulatory network in the Lyme disease spirochete, Borrelia burgdorferi. FEMS Immunol. Med. Microbiol. 58, 285-294. doi: 10.1111/j.1574-695X.2009.00635.x
45. Fries, B. C., Goldman, D. L., Cherniak, R., Ju, R., and Casadevall, A. (1999). Phenotypic switching in Cryptococcus neoformans results in changes in cellular morphology and glucuronoxylomannan structure. Infect. Immun. 67, 6076-6083.
46. Galperin, M. Y. (2004). Bacterial signal transduction network in a genomic perspective. Environ. Microbiol. 6, 552-567. doi: 10.1111/j.1462-2920.2004.00633.x
47. Galperin, M. Y., Natale, D. A., Aravind, L., and Koonin, E. V. (1999). A specialized version of the HD hydrolase domain implicated in signal transduction. J. Mol. Microbiol. Biotechnol. 1, 303-305.
48. Galperin, M. Y., Nikolskaya, A. N., and Koonin, E. V. (2001). Novel domains of the prokaryotic two-component signal transduction systems. FEMS Microbiol. Lett. 203, 11-21. doi: 10.1111/j.1574-6968.2001.tb10814.x
49. Girgis, H. S., Liu, Y., Ryu, W. S., and Tavazoie, S. (2007). A comprehensive genetic characterization of bacterial motility. PLoS Genet. 3:1644-1660. doi: 10.1371/journal.pgen.0030154
50. Goldman, S. R., Sharp, J. S., Vvedenskaya, I. O., Livny, J., Dove, S. L., and Nickels, B. E. (2011). NanoRNAs prime transcription initiation in vivo. Mol. Cell 42, 817-825. doi: 10.1016/j.molcel.2011.06.005
51. Groshong, A. M., and Blevins, J. S. (2014). Insights into the biology of Borrelia burgdorferi gained through the application of molecular genetics. Adv. Appl. Microbiol. 86, 41-143. doi: 10.1016/B978-0-12-800262-9.00002-0
52. Habazettl, J., Allan, M. G., Jenal, U., and Grzesiek, S. (2011). Solution structure of the PilZ domain protein PA4608 complex with cyclic di-GMP identifies charge clustering as molecular readout. J. Biol. Chem. 286, 14304-14314. doi: 10.1074/jbc.M110.209007
53. Hajdušek, O., Síma, R., Ayllón, N., Jalovecká, M., Perner, J., de la Fuente, J., et al. (2013). Interactionof the tick immune system with transmitted pathogens. Front. Cell. Infect. Microbiol. 3:26. doi: 10.3389/fcimb.2013.00026
54. Hammer, B. K., and Bassler, B. L. (2009). Distinct sensory pathways in Vibrio cholerae El Tor and classical biotypes modulate cyclic dimeric GMP levels to control biofilm formation. J. Bacteriol. 191, 169-177. doi: 10.1128/JB.01307-08
55. He, M., Ouyang, Z., Troxell, B., Xu, H., Moh, A., Piesman, J., et al. (2011). Cyclic di-GMP is essential for the survival of the Lyme disease spirochete in ticks. PLoS Pathog. 7:e1002133. doi: 10.1371/journal.ppat.1002133
56. He, M., Zhang, J. J., Ye, M., Lou, Y., and Yang, X. F. (2014). Cyclic Di-GMP receptor PlzA controls virulence gene expression through RpoS in Borrelia burgdorferi. Infect. Immun. 82, 445-452. doi: 10.1128/IAI.01238-13
57. Hengge, R. (2009). Principles of c-di-GMP signalling in bacteria. Nat. Rev. Microbiol. 7, 263-273. doi: 10.1038/nrmicro2109
58. Hickman, J. W., and Harwood, C. S. (2008). Identification of FleQ from Pseudomonas aeruginosa as a c-di-GMP-responsive transcription factor. Mol. Microbiol. 69, 376-389. doi: 10.1111/j.1365-2958.2008.06281.x
59. Hickman, J. W., Tifrea, D. F., and Harwood, C. S. (2005). A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levels. Proc. Natl. Acad. Sci. U.S.A. 102, 14422-14427. doi: 10.1073/pnas.0507170102
60. Hübner, A., Yang, X., Nolen, D. M., Popova, T. G., Cabello, F. C., and 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. doi: 10.1073/pnas.231442498
61. Hyde, J. A., Shaw, D. K., Smith, R. III., Trzeciakowski, J. P., and Skare, J. T. (2009). The BosR regulatory protein of Borrelia burgdorferi interfaces with the RpoS regulatory pathway and modulates both the oxidative stress response and pathogenic properties of the Lyme disease spirochete. Mol. Microbiol. 74, 1344-1355. doi: 10.1111/j.1365-2958.2009.06951.x
62. Hyde, J. A., Shaw, D. K., Smith, R. III., Trzeciakowski, J. P., and Skare, J. T. (2010). Characterization of a conditional bosR mutant in Borrelia burgdorferi. Infect. Immun. 78, 265-274. doi: 10.1128/IAI.01018-09
63. Jenal, U., and Malone, J. (2006). Mechanisms of c-di-GMP signaling in bacteria. Annu. Rev. Genet. 40, 385-407. doi: 10.1128/IAI.01018-09
64. Katona, L. I., Tokarz, R., Kuhlow, C. J., Benach, J., and Benach, J. L. (2004). The fur homologue in Borrelia burgdorferi. J. Bacteriol. 186, 6443-6456. doi: 10.1128/JB.186.19.6443-6456.2004
65. Kazmierczak, M. J., Wiedmann, M., and Boor, K. J. (2005). Alternative sigma factors and their roles in bacterial virulence. Microbiol. Mol. Biol. Rev. 69, 527-543. doi: 10.1128/MMBR.69.4.527-543.2005
66. Kim, Y. R., Lee, S. E., Kim, B., Choy, H., and Rhee, J. H. (2013). A dual regulatory role of cyclic adenosine monophosphate receptor protein in various virulence traits of Vibrio vulnificus. Microbiol. Immunol. 57, 273-280. doi: 10.1111/1348-0421.12031
67. Ko, J., Ryu, K. S., Kim, H., Shin, J. S., Lee, J. O., Cheong, C., et al. (2010). Structure of PP4397 reveals the molecular basis for different c-di-GMP binding modes by PilZ domain proteins. J. Mol. Biol. 398, 97-110. doi: 10.1016/j.jmb.2010.03.007
68. Kostick, J. L., Szkotnicki, L. T., Rogers, E. A., Bocci, P., Raffaelli, N., and Marconi, R. T. (2011). The diguanylate cyclase, Rrp1, regulates critical steps in the enzootic cycle of the Lyme disease spirochetes. Mol. Microbiol. 81, 219-231. doi: 10.1111/j.1365-2958.2011.07687.x
69. Krasteva, P. V., Fong, J. C., Shikuma, N. J., Beyhan, S., Navarro, M. V., Yildiz, F. H., et al. (2010). Vibrio cholerae VpsT regulates matrix production and motility by directly sensing cyclic di-GMP. Science 327, 866-868. doi: 10.1126/science.1181185
70. Kuehn, B. M. (2013). CDC estimates 300,000 US cases of Lyme disease annually. JAMA. 310, 1110. doi: 10.1001/jama.2013.278331
71. Kulasekara, B. R., Kamischke, C., Kulasekara, H. D., Christen, M., Wiggins, P. A., and Miller, S. I. (2013). c-di-GMP heterogeneity is generated by the chemotaxis machinery to regulate flagellar motility. Elife 2, e01402. doi: 10.7554/eLife.01402
72. Lai, T. H., Kumagai, Y., Hyodo, M., Hayakawa, Y., and Rikihisa, Y. (2009). The Anaplasma phagocytophilum PleC histidine kinase and PleD diguanylate cyclase two-component system and role of cyclic Di-GMP in host cell infection. J. Bacteriol. 191, 693-700. doi: 10.1128/JB.01218-08
73. Lane, R. S., Piesman, J., and Burgdorfer, W. (1991). Lyme borreliosis: relation of its causative agent to its vectors and hosts in North America and Europe. Annu. Rev. Entomol. 36, 587-609. doi: 10.1146/annurev.en.36.010191.003103
74. Lee, V. T., Matewish, J. M., Kessler, J. L., Hyodo, M., Hayakawa, Y., and Lory, S. (2007). A c-di- GMP receptor required for bacterial exopolysaccharide production. Mol. Microbiol. 65, 1474-1484. doi: 10.1111/j.1365-2958.2007.05879.x
75. Levine, J. F., Wilson, M. L., and Spielman, A. (1985). Mice as reservoirs of the Lyme disease spirochete. Am. J. Trop. Med. Hyg. 34, 355-360.
76. Li, C., Bakker, R. G., Motaleb, M. A., Sartakova, M. L., Cabello, F. C., and Charon, N. W. (2002). Asymmetrical flagellar rotation in Borrelia burgdorferi nonchemotactic mutants. Proc. Natl. Acad. Sci. U.S.A. 99, 6169-6174. doi: 10.1073/pnas.092010499
77. Luo, Y., Zhou, J., Wang, J., Dayie, T. K., and Sintim, H. O. (2013). Selective binding of 2'-F-c-di-GMP to Ct-E88 and Cb-E43, new class I riboswitches from Clostridium tetani and Clostridium botulinum, respectively. Mol. Biosyst. 9, 1535-1539. doi: 10.1039/c3mb25560c
78. Maes, E., Lecomte, P., and Ray, N. (1998). A cost-of-illness study of Lyme disease in the United States. Clin. Ther. 20, 993-1008. discussion: 992. doi: 10.1016/S0149-2918(98)80081-7
79. Massie, J. P., Reynolds, E. L., Koestler, B. J., Cong, J. P., Agostoni, M., and Waters, C. M. (2012). Quantification of high-specificity cyclic diguanylate signaling. Proc. Natl. Acad. Sci. U.S.A. 109, 12746-12751. doi: 10.1073/pnas.1115663109
80. Mather, T. N., Wilson, M. L., Moore, S. I., Ribeiro, J. M., and Spielman, A. (1989). Comparing the relative potential of rodents as reservoirs of the Lyme disease spirochete (Borrelia burgdorferi). Am. J. Epidemiol. 130, 143-150.
81. McCarthy, Y., Ryan, R. P., O'Donovan, K., He, Y. Q., Jiang, B. L., Feng, J. X., et al. (2008). The role of PilZ domain proteins in the virulence of Xanthomonas campestris pv. campestris. Mol. Plant Pathol. 9, 819-824. doi: 10.1111/j.1364-3703.2008.00495.x
82. Merighi, M., Lee, V. T., Hyodo, M., Hayakawa, Y., and Lory, S. (2007). The second messenger bis-(3'-5')-cyclic-GMP and its PilZ domain-containing receptor Alg44 are required for alginate biosynthesis in Pseudomonas aeruginosa. Mol. Microbiol. 65, 876-895. doi: 10.1111/j.1365-2958.2007.05817.x
83. Monds, R. D., Newell, P. D., Gross, R. H., and O'Toole, G. A. (2007). Phosphate-dependent modulation of c-di-GMP levels regulates Pseudomonas fluorescens Pf0-1 biofilm formation by controlling secretion of the adhesin LapA. Mol. Microbiol. 63, 656-679. doi: 10.1111/j.1365-2958.2006.05539.x
84. Moriarty, T. J., Norman, M. U., Colarusso, P., Bankhead, T., Kubes, P., and Chaconas, G. (2008). Real-time high resolution 3D imaging of the Lyme disease spirochete adhering to and escaping from the vasculature of a living host. PLoS Pathog. 4:e1000090. doi: 10.1371/journal.ppat.1000090
85. Motaleb, M. A., Miller, M. R., Li, C., Bakker, R. G., Goldstein, S. F., Silversmith, R. E., et al. (2005). CheX is a phosphorylated CheY phosphatase essential for Borrelia burgdorferi chemotaxis. J. Bacteriol. 187, 7963-7969. doi: 10.1128/JB.187.23.7963-7969.2005
86. Motaleb, M. A., Sultan, S. Z., Miller, M. R., Li, C., and Charon, N. W. (2011). CheY3 of Borrelia burgdorferi is the key response regulator essential for chemotaxis and forms a long-lived phosphorylated intermediate. J. Bacteriol. 193, 3332-3341. doi: 10.1128/JB.00362-11
87. Nickels, B. E. (2012). A new way to start: nanoRNA-mediated priming of transcription initiation. Transcription 3, 300-304. doi: 10.4161/trns.21903
88. Norman, M. U., Moriarty, T. J., Dresser, A. R., Millen, B., Kubes, P., and Chaconas, G. (2008). Molecular mechanisms involved in vascular interactions of the Lyme disease pathogen in a living host. PLoS Pathog. 4:e1000169. doi: 10.1371/journal.ppat.1000169
89. Ojaimi, C., Brooks, C., Akins, D., Casjens, S., Rosa, P., Elias, A., et al. (2002). Borrelia burgdorferi gene expression profiling with membrane-based arrays. Meth. Enzymol. 358, 165-177. doi: 10.1016/S0076-6879(02)58088-5
90. Ojaimi, C., Brooks, C., Casjens, S., Rosa, P., Elias, A., Barbour, A., et al. (2003). Profiling of temperature-induced changes in Borrelia burgdorferi gene expression by using whole genome arrays. Infect. Immun. 71, 1689-1705. doi: 10.1128/IAI.71.4.1689-1705.2003
91. Ostfeld, R. S. (1997). The ecology of Lyme-disease risk: complex interactions between seemingly unconnected phenomena determine risk of exposure to this expanding disease. Am. Sci. 85, 338-346.
92. Ouyang, Z., Blevins, J. S., and Norgard, M. V. (2008). Transcriptional interplay among the regulators Rrp2, RpoN, and RpoS in Borrelia burgdorferi. Microbiology 154, 2641-2658. doi: 10.1099/mic.0.2008/019992-0
93. Ouyang, Z., Deka, R. K., and Norgard, M. V. (2011). BosR (BB0647) controls the RpoN-RpoS regulatory pathway and virulence expression in Borrelia burgdorferi by a novel DNA- binding mechanism. PLoS Pathog. 7:e1001272. doi: 10.1371/journal.ppat.1001272
94. Ouyang, Z., Kumar, M., Kariu, T., Haq, S., Goldberg, M., Pal, U., et al. (2009). BosR (BB0647) governs virulence expression in Borrelia burgdorferi. Mol. Microbiol. 74,1331-1343. doi: 10.1111/j.1365-2958.2009.06945.x
95. Ouyang, Z., Narasimhan, S., Neelakanta, G., Kumar, M., Pal, U., Fikrig, E., et al. (2012). Activation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi. BMC Microbiol. 12:44. doi: 10.1186/1471-2180-12-44
96. Pappas, C. J., Iyer, R., Petzke, M. M., Caimano, M. J., Radolf, J. D., and Schwartz, I. (2011). Borrelia burgdorferi requires glycerol for maximum fitness during the tick phase of the enzootic cycle. PLoS Pathog. 7:e1002102. doi: 10.1371/journal.ppat.1002102
97. Paul, K., Nieto, V., Carlquist, W. C., Blair, D. F., and Harshey, R. M. (2010). The c-di-GMP binding protein YcgR controls flagellar motor direction and speed to affect chemotaxis by a "backstop brake" mechanism. Mol. Cell 38, 128-139. doi: 10.1016/j.molcel.2010.03.001
98. Paul, R., Weiser, S., Amiot, N. C., Chan, C., Schirmer, T., Giese, B., et al. (2004). Cell cycle-dependent dynamic localization of a bacterial response regualtor with a novel di-guanylate cyclase output domain. Genes Dev. 18, 715-727. doi: 10.1101/gad.289504
99. Pazy, Y., Motaleb, M. A., Guarnieri, M. T., Charon, N. W., Zhao, R., and Silversmith, R. E. (2010). Identical phosphatase mechanisms achieved through distinct modes of binding phosphoprotein substrate. Proc. Natl. Acad. Sci. U.S.A. 107, 1924-1929. doi: 10.1073/pnas.0911185107
100. Pesavento, C., Becker, G., Sommerfeldt, N., Possling, A., Tschowri, N., Mehlis, A., et al. (2008). Inverse regulatory coordination of motility and curli-mediated adhesion in Escherichia coli. Genes Dev. 22, 2434-2446. doi: 10.1101/gad.475808
101. Pitzer, J. E., Sultan, S. Z., Hayakawa, Y., Hobbs, G., Miller, M. R., and Motaleb, M. A. (2011). Analysis of the Borrelia burgdorferi c-di-GMP-binding protein PlzA reveals a role in motility and virulence. Infect. Immun. 79, 1815-1825. doi: 10.1128/IAI.00075-11
102. Pratt, J. T., Tamayo, R., Tischler, A. D., and Camilli, A. (2007). PilZ domain proteins bind cyclic diguanylate and regulate diverse processes in Vibrio cholerae. J. Biol. Chem. 282, 12860-12870. doi: 10.1074/jbc.M611593200
103. Radolf, J. D., Caimano, M. J., Stevenson, B., and Hu, L. T. (2012). Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochetes. Nat. Rev. Microbiol. 10, 87-99. doi: 10.1038/nrmicro2714
104. Revel, A. T., Talaat, A. M., and Norgard, M. V. (2002). DNA microarray analysis of differential gene expression in Borrelia burgdorferi, the Lyme disease spirochete. Proc. Natl. Acad. Sci. U.S.A. 99, 1562-1567. doi: 10.1073/pnas.032667699
105. Rogers, E. A., Terekhova, D., Zhang, H. M., Hovis, K. M., Schwartz, I., and Marconi, R. T. (2009). Rrp1, a c-di-GMP-producing response regulator, is an important regulator of Borrelia burgdorferi core cellular functions. Mol. Microbiol. 71, 1551-1573. doi: 10.1111/j.1365-2958.2009.06621.x
106. Römling, U. (2005). Characterization of the rdar morphotype, a multicellular behaviour in Enterobacteriaceae. Cell. Mol. Life Sci. 62, 1234-1246. doi: 10.1007/s00018-005-4557-x
107. Römling, U., Galperin, M. Y., and Gomelsky, M. (2013). Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. Microbiol. Mol. Biol. Rev. 77, 1-52. doi: 10.1128/MMBR.00043-12
108. Römling, U., Gomelsky, M., and Galperin, M. Y. (2005). C-di-GMP: the dawning of a novel bacterial signalling system. Mol. Microbiol. 57, 629-639. doi: 10.1111/j.1365-2958.2005.04697.x
109. Römling, U., and Simm, R. (2009). Prevailing concepts of c-di-GMP signaling. Contrib. Microbiol. 16, 161-181. doi: 10.1159/000219379
110. Ross, P., Weinhouse, H., Aloni, Y., Michaeli, D., Weinberger-Ohana, P., Mayer, R., et al. (1987). Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid. Nature 325, 279-281. doi: 10.1038/325279a0
111. Russell, M. H., Bible, A. N., Fang, X., Gooding, J. R., Campagna, S. R., Gomelsky, M., et al. (2013). Integration of the second messenger c-di-GMP into the chemotactic signaling pathway. MBio 4, e00001-e00013. doi: 10.1128/mBio.00001-13
112. Ryan, R. P., Fouhy, Y., Lucey, J. F., Crossman, L. C., Spiro, S., He, Y. W., et al. (2006a). Cell-cell signaling in Xanthomonas campetris involves an HD-GYP domain protein that functions in cyclic di-GMP turnover. Proc. Natl. Acad. Sci. U.S.A. 103, 6712-6717. doi: 10.1073/pnas.0600345103
113. Ryan, R. P., Fouhy, Y., Lucey, J. F., and Dow, J. M. (2006b). Cyclic di-GMP signaling in bacteria: recent advances and new puzzles. J. Bacteriol. 188, 8327-8334. doi: 10.1128/JB.01079-06
114. Ryan, R. P., Fouhy, Y., Lucey, J. F., Jiang, B. L., He, Y. Q., Feng, J. X., et al. (2007). Cyclic-di-GMP signalling in the virulence and enviromental adaptation of Xanthomonas campetris. Mol. Microbiol. 63, 429-442. doi: 10.1111/j.1365-2958.2006.05531.x
115. Ryan, R. P., Lucey, J., O'Donovan, K., McCarthy, Y., Yang, L., Toker-Nielson, T., et al. (2009). HD-GYP domain proteins regulate biofilm formation and virulence in Pseduomonas aeruginosa. Environ. Microbiol. 11, 1126-1136. doi: 10.1111/j.1462-2920.2008.01842.x
116. Ryan, R. P., McCarthy, Y., Andrade, M., Farah, C. S., Armitage, J. P., and Dow, J. M. (2010). Cell-cell signal-dependent dynamic interactions between HD-GYP and GGDEF domain proteins mediate virulence in Xanthomonas campestris. Proc. Natl. Acad. Sci. U.S.A. 107, 5989-5994. doi: 10.1073/pnas.0912839107
117. Ryjenkov, D. A., Simm, R., Römling, U., and 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. doi: 10.1074/jbc.C600179200
118. Ryjenkov, D. A., Tarutina, M., Moskvin, O. V., and 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. doi: 10.1128/JB.187.5.1792-1798.2005
119. Samuels, D. S. (2011). Gene regulation in Borrelia burgdorferi. Annu. Rev. Microbiol. 65, 479-499. doi: 10.1146/annurev.micro.112408.134040
120. Samuels, D. S., and Radolf, J. D. (2009). Who is the BosR around here anyway? Mol. Microbiol. 74, 1295-1299. doi: 10.1111/j.1365-2958.2009.06971.x
121. Schirmer, T., and Jenal, U. (2009). Structural and mechanistic determinants of c-di-GMP signalling. Nat. Rev. Microbiol. 7, 724-735. doi: 10.1038/nrmicro2203
122. Schmidt, A. J., Ryjenkov, D. A., and Gomelsky, M. (2005). The ubiquitous protein domain EAL is a cyclic diguanylate-specific phosphodiesterase: enzymatically active and inactive EAL domains. J. Bacteriol. 187, 4774-4781. doi: 10.1128/JB.187.14.4774-4781.2005
123. Schmidt, K. A., and Ostfeld, R. S. (2001). Biodiversity and the dilution effect in disease ecology. Ecology 82, 609-619. doi: 10.1890/0012-9658(2001)082[0609:BATDEI]2.0.CO;2
124. Seshu, J., Boylan, J. A., Hyde, J. A., Swingle, K. L., Gherardini, F. C., and Skare, J. T. (2004). A conservative amino acid change alters the function of BosR, the redox regulator of Borrelia burgdorferi. Mol. Microbiol. 54, 1352-1363. doi: 10.1111/j.1365-2958.2004.04352.x
125. Silversmith, R. E., and Bourret, R. B. (1999). Throwing the switch in bacterial chemotaxis. Trends Microbiol. 7, 16-22. doi: 10.1016/S0966-842X(98)01409-7
126. Smith, K. D., Lipchock, S. V., Ames, T. D., Wang, J., Breaker, R. R., and Strobel, S. A. (2009). Structural basis of ligand binding by a c-di-GMP riboswitch. Nat. Struct. Mol. Biol. 16, 1218-1223. doi: 10.1038/nsmb.1702
127. Sommerfeldt, N., Possling, A., Becker, G., Pesavento, C., Tschowri, N., and Hengge, R. (2009). Gene expression patterns and differential input into curli fimbriae regulation of all GGDEF/EAL domain proteins in Escherichia coli. Microbiology 155, 1318-1331. doi: 10.1099/mic.0.024257-0
128. Sonenshine, D. E., Ceraul, S. M., Hynes, W. E., Macaluso, K. R., and Azad, A. F. (2002). Expression of defensin-like peptides in tick hemolymph and midgut in response to challenge with Borrelia burgdorferi, Escherichia coli, and Bacillus subtilis. Exp. Appl. Acarol. 28, 127-134. doi: 10.1023/A:1025354326877
129. Sonenshine, D. E., and Hynes, W. L. (2008). Molecular characterization and related aspects of the innate immune response in ticks. Front. Biosci. 13, 7046-7063. doi: 10.2741/3209
130. Stelitano, V., Giardina, G., Paiardini, A., Castiglione, N., Cutruzzolà, F., and Rinaldo, S. (2013). C-di-GMP hydrolysis by Pseudomonas aeruginosa HD-GYP phosphodiesterases: analysis of the reaction mechanism and novel roles for pGpG. PLoS ONE 8:e74920. doi: 10.1371/journal.pone.0074920
131. Stock, A. M., Robinson, V. L., and Goudreau, P. N. (2000). Two-component signal transduction. Annu. Rev. Biochem. 69, 183-215. doi: 10.1146/annurev.biochem.69.1.183
132. Sudarsan, N., Lee, E. R., Weinberg, Z., Moy, R. H., Kim, J. N., Link, K. H., et al. (2008). Riboswitches in eubacteria sense the second messenger cyclic di-GMP. Science 321, 411-413. doi: 10.1126/science.1159519
133. Sultan, S. Z., Pitzer, J. E., Boquoi, T., Hobbs, G., Miller, M. R., and Motaleb, M. A. (2011). Analysis of the HD-GYP domain cyclic dimeric GMP phosphodiesterase reveals a role in motility and the enzootic life cycle of Borrelia burgdorferi. Infect. Immun. 79, 3273-3283. doi: 10.1128/IAI.05153-11
134. Sultan, S. Z., Pitzer, J. E., Miller, M. R., and Motaleb, M. A. (2010). Analysis of a Borrelia burgdorferi phosphodiesterase demonstrates a role for cyclic-di-guanosine monophosphate in motility and virulence. Mol. Microbiol. 77, 128-142. doi: 10.1111/j.1365-2958.2010.07191.x
135. Sze, C. W., Smith, A., Choi, Y. H., Yang, X., Pal, U., Yu, A., et al. (2013). Study of the response regulator Rrp1 reveals its regulatory role in chitobiose utilization and virulence of Borrelia burgdorferi. Infect. Immun. 81, 1775-1787. doi: 10.1128/IAI.00050-13
136. Sze, C. W., Zhang, K., Kariu, T., Pal, U., and Li, C. (2012). Borrelia burgdorferi needs chemotaxis to establish infection in mammals and to accomplish its enzootic cycle. Infect. Immun. 80, 2485-2492. doi: 10.1128/IAI.00145-12
137. Tal, R., Wong, H. C., Calhoon, R., Gelfand, D., Fear, A. L., Volman, G., et al. (1998). Three cdg operons control cellular turnover of cyclic di-GMP in Acetobacter xylinum: genetic organization and occurrence of conserved domains in isoenzymes. J. Bacteriol. 180, 4416-4425.
138. Tam, R., and Saier, M. H. (1999). Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria. Microbiol. Rev. 57, 320-346.
139. Tamayo, R., Pratt, J. T., and Camilli, A. (2007). Roles of cyclic diguanylate in the regulation of bacterial pathogenesis. Annu. Rev. Microbiol. 61, 131-148. doi: 10.1146/annurev.micro.61.080706.093426
140. Tamayo, R., Schild, S., Pratt, J. T., and Camilli, A. (2008). Role of cyclic Di-GMP during El Tor biotype Vibrio cholerae infection: characterization of the in vivo-induced cyclic Di-GMP phosphodiesterase CdpA. Infect. Immun. 76, 1617-1627. doi: 10.1128/IAI.01337-07
141. Tamayo, R., Tischler, A. D., and Camilli, A. (2005). The EAL domain protein VieA is a cyclic diguanylate phosphodiesterase. J. Biol. Chem. 280, 33324-33330. doi: 10.1074/jbc.M506500200
142. Tao, F., He, Y. W., Wu, D. H., Swarup, S., and Zhang, L. H. (2010). The cyclic nucleotide monophosphate domain of Xanthomonas campestris global regulator Clp defines a new class of cyclic di-GMP effectors. J. Bacteriol. 192, 1020-1029. doi: 10.1128/JB.01253-09
143. Thomas, C., Andersson, C. R., Canales, S. R., and Golden, S. S. (2004). PsfR, a factor that stimulates psbAI expression in the cyanobacterium Synechococcus elongatus PCC 7942. Microbiology 150, 1031-1040. doi: 10.1099/mic.0.26915-0
144. Tilly, K., Rosa, P. A., and Stewart, P. E. (2008). Biology of infection with Borrelia burgdorferi. Infect. Dis. Clin. North Am. 22, 217-234. doi: 10.1016/j.idc.2007.12.013
145. Tokarz, R., Anderton, J. M., Katona, L. I., and Benach, J. L. (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. doi: 10.1128/IAI.72.9.5419-5432.2004
146. Trappetti, C., Ogunniyi, A. D., Oggioni, M. R., and Paton, J. C. (2011). Extracellular matrix formation enhances the ability of Streptococcus pneumoniae to cause invasive disease. PLoS ONE 6:e19844. doi: 10.1371/journal.pone.0019844
147. Tsao, J. I. (2009). Reviewing molecular adaptations of Lyme borreliosis spirochetes in the context of reproductive fitness in natural transmission cycles. Vet. Res. 40:36. doi: 10.1051/vetres/2009019
148. Tuckerman, J. R., Gonzalez, G., and Gilles-Gonzalez, M. A. (2011). Cyclic di-GMP activation of polynucleotide phosphorylase signal-dependent RNA processing. J. Mol. Biol. 407, 633-639. doi: 10.1016/j.jmb.2011.02.019
149. Tuckerman, J. R., Gonzalez, G., Sousa, E. H., Wan, X., Saito, J. A., Alam, M., et al. (2009). An oxygen-sensing diguanylate cyclase and phosphodiesterase couple for c-di-GMP control. Biochemistry 48, 9764-9774. doi: 10.1021/bi901409g
150. Vvedenskaya, I. O., Sharp, J. S., Goldman, S. R., Kanabar, P. N., Livny, J., Dove, S. L., et al. (2012). Growth phase-dependent control of transcription start site selection and gene expression by nanoRNAs. Genes Dev. 26, 1498-1507. doi: 10.1101/gad.192732.112
151. Weber, H., Pesavento, C., Possling, A., Tischendorf, G., and Hengge, R. (2006). Cyclic-di-GMP-mediated signalling within the sigma network of Escherichia coli. Mol. Microbiol. 62, 1014-1034. doi: 10.1111/j.1365-2958.2006.05440.x
152. West, A. H., and Stock, A. M. (2001). Histidine kinases and response regulator proteins in two-component signaling systems. Trends Biochem. Sci. 26, 369-376. doi: 10.1016/S0968-0004(01)01852-7
153. Wolfe, A. J., and Visick, K. L. (2008). Get the message out: c-di-GMP regulates multiple levels of flagellum-based motility. J. Bacteriol. 190, 463-475. doi: 10.1128/JB.01418-07
154. Xu, H., Caimano, M. J., Lin, T., He, M., Radolf, J. D., Norris, S. J., et al. (2010). Role of acetyl-phosphate in activation of the Rrp2-RpoN-RpoS pathway in Borrelia burgdorferi. PLoS Pathog. 6:e1001104. doi: 10.1371/journal.ppat.1001104
155. Yang, X. F., Alani, S. M., and Norgard, M. V. (2003a). The response regulator Rrp2 is essential for the expression of major membrane lipoproteins in Borrelia burgdorferi. Proc. Natl. Acad. Sci. U.S.A. 100, 11001-11006. doi: 10.1073/pnas.1834315100
156. Yang, X. F., Hübner, A., Popova, T. G., Hagman, K. E., and Norgard, M. V. (2003b). Regulation of expression of the paralogous Mlp family in Borrelia burgdorferi. Infect. Immun. 71, 5012-5020. doi: 10.1128/IAI.71.9.5012-5020.2003
157. Yildiz, F. H., and Schoolnik, G. K. (1999). Vibrio cholerae O1 El Tor: identification of a gene cluster required for the rugose colony type, exopolysaccharide production, chlorine resistance, and biofilm formation. Proc. Natl. Acad. Sci. U.S.A. 96, 4028-4033. doi: 10.1073/pnas.96.7.4028
158. Yildiz, F. H., and Visick, K. L. (2009). Vibrio biofilms: so much the same yet so different. Trends Microbiol. 17, 109-118. doi: 10.1016/j.tim.2008.12.004
159. Zhang, X., Meltzer, M. I., Peña, C. A., Hopkins, A. B., Wroth, L., and Fix, A. D. (2006). Economic impact of Lyme disease. Emerg. Infect. Dis. 12, 653-660. doi: 10.3201/eid1204.050602
160. Zorraquino, V., Garcia, B., Latasa, C., Echeverz, M., Toledo-Arana, A., Valle, J., et al. (2013). Coordinated c-di-GMP repression of Salmonella motility through YcgR and cellulose. J. Bacteriol. 195, 417-428. doi: 10.1128/JB.01789-12