Signals Modulating Cyclic di-GMP Pathways in Vibrio cholerae

  • Erin Young
  • Garett Bonds
  • Ece KaratanEmail author


Vibrio cholerae is an aquatic bacterium that is also the causative agent of the diarrheal disease cholera. In this bacterium, the secondary messenger, cyclic di-GMP, regulates the lifestyle transition between a motile state and a sessile biofilm state as well as other key processes such as virulence factor production. The V. cholerae genome encodes 62 proteins that contain GGDEF, EAL, or HD-GYP domains that are predicted to be involved in the synthesis or degradation of cyclic di-GMP. Presumably, one or more signals modulate the activity of each of these proteins to regulate cyclic di-GMP levels in the cell; however, to date, only a few of these signals have been elucidated. In this chapter, we present our current knowledge about the signals that have an effect on cyclic di-GMP signaling in V. cholerae and the signaling networks that play direct or indirect roles in processing these signals. These signals include polyamines, bile acids, temperature, and molecular oxygen. We also discuss how cyclic di-GMP signaling networks interact with other signal transduction pathways, such as quorum sensing, to regulate behavior. In addition to the many unidentified signals, there are other gaps in our knowledge including how signal specificity and processing is achieved and what is the nature and the extent of crosstalk among cyclic di-GMP and other signal transduction networks. Future research addressing these questions will help us better understand how V. cholerae assimilates cues in both aquatic habitats and host organisms to optimize its response to specific environments through cyclic di-GMP signaling.


Vibrio cholerae Cyclic di-GMP Polyamines Biofilm Motility Virulence 


  1. 1.
    Prouty MG, Correa NE, Klose KE (2001) The novel sigma54- and sigma28-dependent flagellar gene transcription hierarchy of Vibrio cholerae. Mol Microbiol 39(6):1595–1609CrossRefGoogle Scholar
  2. 2.
    Karatan E, Watnick P (2009) Signals, regulatory networks, and materials that build and break bacterial biofilms. Microbiol Mol Biol Rev 73(2):310–347. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kaper JB, Morris JG Jr, Levine MM (1995) Cholera. Clin Microbiol Rev 8(1):48–86CrossRefGoogle Scholar
  4. 4.
    Herrington DA, Hall RH, Losonsky G, Mekalanos JJ, Taylor RK, Levine MM (1988) Toxin, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans. J Exp Med 168(4):1487–1492CrossRefGoogle Scholar
  5. 5.
    Thelin KH, Taylor RK (1996) Toxin-coregulated pilus, but not mannose-sensitive hemagglutinin, is required for colonization by Vibrio cholerae O1 El Tor biotype and O139 strains. Infect Immun 64(7):2853–2856CrossRefGoogle Scholar
  6. 6.
    Tamayo R, Patimalla B, Camilli A (2010) Growth in a biofilm induces a hyperinfectious phenotype in Vibrio cholerae. Infect Immun 78(8):3560–3569. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Tischler AD, Camilli A (2005) Cyclic diguanylate regulates Vibrio cholerae virulence gene expression. Infect Immun 73(9):5873–5882. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Tischler AD, Camilli A (2004) Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation. Mol Microbiol 53(3):857–869. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Romling U, Galperin MY, Gomelsky M (2013) Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. Microbiol Mol Biol Rev 77(1):1–52. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Schild S, Tamayo R, Nelson EJ, Qadri F, Calderwood SB, Camilli A (2007) Genes induced late in infection increase fitness of Vibrio cholerae after release into the environment. Cell Host Microbe 2(4):264–277. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Hall-Stoodley L, Costerton JW, Stoodley P (2004) Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol 2(2):95–108. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Costerton JW, Lewandowski Z, Caldwell DE, Korber DR, Lappin-Scott HM (1995) Microbial biofilms. Annu Rev Microbiol 49:711–745. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Davey ME, O’Toole GA (2000) Microbial biofilms: from ecology to molecular genetics. Microbiol Mol Biol Rev 64(4):847–867CrossRefGoogle Scholar
  14. 14.
    Donlan RM, Costerton JW (2002) Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 15(2):167–193CrossRefGoogle Scholar
  15. 15.
    Matz C, McDougald D, Moreno AM, Yung PY, Yildiz FH, Kjelleberg S (2005) Biofilm formation and phenotypic variation enhance predation-driven persistence of Vibrio cholerae. Proc Natl Acad Sci USA 102(46):16819–16824. CrossRefPubMedGoogle Scholar
  16. 16.
    Zhu J, Mekalanos JJ (2003) Quorum sensing-dependent biofilms enhance colonization in Vibrio cholerae. Dev Cell 5(4):647–656CrossRefGoogle Scholar
  17. 17.
    Watnick PI, Fullner KJ, Kolter R (1999) A role for the mannose-sensitive hemagglutinin in biofilm formation by Vibrio cholerae El Tor. J Bacteriol 181(11):3606–3609CrossRefGoogle Scholar
  18. 18.
    Beyhan S, Tischler AD, Camilli A, Yildiz FH (2006) Transcriptome and phenotypic responses of Vibrio cholerae to increased cyclic di-GMP level. J Bacteriol 188(10):3600–3613. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Jones CJ, Utada A, Davis KR, Thongsomboon W, Zamorano Sanchez D, Banakar V, Cegelski L, Wong GC, Yildiz FH (2015) C-di-GMP regulates motile to sessile transition by modulating MshA pili biogenesis and near-surface motility behavior in Vibrio cholerae. PLoS Pathog 11(10):e1005068. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Roelofs KG, Jones CJ, Helman SR, Shang X, Orr MW, Goodson JR, Galperin MY, Yildiz FH, Lee VT (2015) Systematic identification of cyclic-di-GMP binding proteins in Vibrio cholerae reveals a novel class of cyclic-di-GMP-binding ATPases associated with type II secretion systems. PLoS Pathog 11(10):e1005232. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Wang YC, Chin KH, Tu ZL, He J, Jones CJ, Sanchez DZ, Yildiz FH, Galperin MY, Chou SH (2016) Nucleotide binding by the widespread high-affinity cyclic di-GMP receptor MshEN domain. Nat Commun 7:12481. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Watnick PI, Kolter R (1999) Steps in the development of a Vibrio cholerae El Tor biofilm. Mol Microbiol 34(3):586–595CrossRefGoogle Scholar
  23. 23.
    Yildiz FH, Schoolnik GK (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 USA 96(7):4028–4033CrossRefGoogle Scholar
  24. 24.
    Fong JC, Karplus K, Schoolnik GK, Yildiz FH (2006) Identification and characterization of RbmA, a novel protein required for the development of rugose colony morphology and biofilm structure in Vibrio cholerae. J Bacteriol 188(3):1049–1059. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Fong JC, Yildiz FH (2007) The rbmBCDEF gene cluster modulates development of rugose colony morphology and biofilm formation in Vibrio cholerae. J Bacteriol 189(6):2319–2330. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Moorthy S, Watnick PI (2005) Identification of novel stage-specific genetic requirements through whole genome transcription profiling of Vibrio cholerae biofilm development. Mol Microbiol 57(6):1623–1635. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Beyhan S, Yildiz FH (2007) Smooth to rugose phase variation in Vibrio cholerae can be mediated by a single nucleotide change that targets c-di-GMP signalling pathway. Mol Microbiol 63(4):995–1007. CrossRefPubMedGoogle Scholar
  28. 28.
    Casper-Lindley C, Yildiz FH (2004) VpsT is a transcriptional regulator required for expression of vps biosynthesis genes and the development of rugose colonial morphology in Vibrio cholerae O1 El Tor. J Bacteriol 186(5):1574–1578CrossRefGoogle Scholar
  29. 29.
    Zamorano-Sanchez D, Fong JC, Kilic S, Erill I, Yildiz FH (2015) Identification and characterization of VpsR and VpsT binding sites in Vibrio cholerae. J Bacteriol 197(7):1221–1235. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Yildiz FH, Dolganov NA, Schoolnik GK (2001) VpsR, a member of the response regulators of the two-component regulatory systems, is required for expression of vps biosynthesis genes and EPS(ETr)-associated phenotypes in Vibrio cholerae O1 El Tor. J Bacteriol 183(5):1716–1726. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Krasteva PV, Fong JC, Shikuma NJ, Beyhan S, Navarro MV, Yildiz FH, Sondermann H (2010) Vibrio cholerae VpsT regulates matrix production and motility by directly sensing cyclic di-GMP. Science 327(5967):866–868. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Srivastava D, Harris RC, Waters CM (2011) Integration of cyclic di-GMP and quorum sensing in the control of vpsT and aphA in Vibrio cholerae. J Bacteriol 193(22):6331–6341. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Hsieh ML, Hinton DM, Waters CM (2018) VpsR and cyclic di-GMP together drive transcription initiation to activate biofilm formation in Vibrio cholerae. Nucleic Acids Res 46(17):8876–8887. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Beyhan S, Odell LS, Yildiz FH (2008) Identification and characterization of cyclic diguanylate signaling systems controlling rugosity in Vibrio cholerae. J Bacteriol 190(22):7392–7405. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Lim B, Beyhan S, Meir J, Yildiz FH (2006) Cyclic-diGMP signal transduction systems in Vibrio cholerae: modulation of rugosity and biofilm formation. Mol Microbiol 60(2):331–348. CrossRefPubMedGoogle Scholar
  36. 36.
    Liu X, Beyhan S, Lim B, Linington RG, Yildiz FH (2010) Identification and characterization of a phosphodiesterase that inversely regulates motility and biofilm formation in Vibrio cholerae. J Bacteriol 192(18):4541–4552. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Conner JG, Zamorano-Sanchez D, Park JH, Sondermann H, Yildiz FH (2017) The ins and outs of cyclic di-GMP signaling in Vibrio cholerae. Curr Opin Microbiol 36:20–29. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Correa NE, Lauriano CM, McGee R, Klose KE (2000) Phosphorylation of the flagellar regulatory protein FlrC is necessary for Vibrio cholerae motility and enhanced colonization. Mol Microbiol 35(4):743–755CrossRefGoogle Scholar
  39. 39.
    Srivastava D, Hsieh ML, Khataokar A, Neiditch MB, Waters CM (2013) Cyclic di-GMP inhibits Vibrio cholerae motility by repressing induction of transcription and inducing extracellular polysaccharide production. Mol Microbiol 90(6):1262–1276. CrossRefPubMedGoogle Scholar
  40. 40.
    Amikam D, Galperin MY (2006) PilZ domain is part of the bacterial c-di-GMP binding protein. Bioinformatics 22(1):3–6. CrossRefGoogle Scholar
  41. 41.
    Pratt JT, Tamayo R, Tischler AD, Camilli A (2007) PilZ domain proteins bind cyclic diguanylate and regulate diverse processes in Vibrio cholerae. J Biol Chem 282(17):12860–12870. CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Sudarsan N, Lee ER, Weinberg Z, Moy RH, Kim JN, Link KH, Breaker RR (2008) Riboswitches in eubacteria sense the second messenger cyclic di-GMP. Science 321(5887):411–413. CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Pursley BR, Maiden MM, Hsieh ML, Fernandez NL, Severin GB, Waters CM (2018) Cyclic di-GMP regulates TfoY in Vibrio cholerae to control motility by both transcriptional and posttranscriptional mechanisms. J Bacteriol 200(7).
  44. 44.
    Metzger LC, Stutzmann S, Scrignari T, Van der Henst C, Matthey N, Blokesch M (2016) Independent regulation of type VI secretion in Vibrio cholerae by TfoX and TfoY. Cell Rep 15(5):951–958. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Syed KA, Beyhan S, Correa N, Queen J, Liu J, Peng F, Satchell KJ, Yildiz F, Klose KE (2009) The Vibrio cholerae flagellar regulatory hierarchy controls expression of virulence factors. J Bacteriol 191(21):6555–6570. CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Krebs SJ, Taylor RK (2011) Protection and attachment of Vibrio cholerae mediated by the toxin-coregulated pilus in the infant mouse model. J Bacteriol 193(19):5260–5270. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Chinnapen DJ, Chinnapen H, Saslowsky D, Lencer WI (2007) Rafting with cholera toxin: endocytosis and trafficking from plasma membrane to ER. FEMS Microbiol Lett 266(2):129–137. CrossRefPubMedGoogle Scholar
  48. 48.
    King CA, Van Heyningen WE (1973) Deactivation of cholera toxin by a sialidase-resistant monosialosylganglioside. J Infect Dis 127(6):639–647CrossRefGoogle Scholar
  49. 49.
    Moss J, Vaughan M (1977) Mechanism of action of choleragen. Evidence for ADP-ribosyltransferase activity with arginine as an acceptor. J Biol Chem 252(7):2455–2457PubMedGoogle Scholar
  50. 50.
    Peterson JW, Hejtmancik KE, Markel DE, Craig JP, Kurosky A (1979) Antigenic specificity of neutralizing antibody to cholera toxin. Infect Immun 24(3):774–779CrossRefGoogle Scholar
  51. 51.
    DiRita VJ, Parsot C, Jander G, Mekalanos JJ (1991) Regulatory cascade controls virulence in Vibrio cholerae. Proc Natl Acad Sci USA 88(12):5403–5407CrossRefGoogle Scholar
  52. 52.
    Higgins DE, Nazareno E, DiRita VJ (1992) The virulence gene activator ToxT from Vibrio cholerae is a member of the AraC family of transcriptional activators. J Bacteriol 174(21):6974–6980CrossRefGoogle Scholar
  53. 53.
    Kovacikova G, Skorupski K (2001) Overlapping binding sites for the virulence gene regulators AphA, AphB and cAMP-CRP at the Vibrio cholerae tcpPH promoter. Mol Microbiol 41(2):393–407CrossRefGoogle Scholar
  54. 54.
    Hase CC, Mekalanos JJ (1998) TcpP protein is a positive regulator of virulence gene expression in Vibrio cholerae. Proc Natl Acad Sci USA 95(2):730–734CrossRefGoogle Scholar
  55. 55.
    Krukonis ES, Yu RR, Dirita VJ (2000) The Vibrio cholerae ToxR/TcpP/ToxT virulence cascade: distinct roles for two membrane-localized transcriptional activators on a single promoter. Mol Microbiol 38(1):67–84CrossRefGoogle Scholar
  56. 56.
    Tischler AD, Lee SH, Camilli A (2002) The Vibrio cholerae vieSAB locus encodes a pathway contributing to cholera toxin production. J Bacteriol 184(15):4104–4113CrossRefGoogle Scholar
  57. 57.
    Martinez-Wilson HF, Tamayo R, Tischler AD, Lazinski DW, Camilli A (2008) The Vibrio cholerae hybrid sensor kinase VieS contributes to motility and biofilm regulation by altering the cyclic diguanylate level. J Bacteriol 190(19):6439–6447. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Dey AK, Bhagat A, Chowdhury R (2013) Host cell contact induces expression of virulence factors and VieA, a cyclic di-GMP phosphodiesterase, in Vibrio cholerae. J Bacteriol 195(9):2004–2010. CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Beyhan S, Tischler AD, Camilli A, Yildiz FH (2006) Differences in gene expression between the classical and El Tor biotypes of Vibrio cholerae O1. Infect Immun 74(6):3633–3642. CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Kariisa AT, Grube A, Tamayo R (2015) Two nucleotide second messengers regulate the production of the Vibrio cholerae colonization factor GbpA. BMC Microbiol 15:166. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Reidl J, Klose KE (2002) Vibrio cholerae and cholera: out of the water and into the host. FEMS Microbiol Rev 26(2):125–139. CrossRefPubMedGoogle Scholar
  62. 62.
    Kariisa AT, Weeks K, Tamayo R (2016) The RNA domain Vc1 regulates downstream gene expression in response to cyclic diguanylate in Vibrio cholerae. PLoS One 11(2):e0148478. CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Johnson TL, Fong JC, Rule C, Rogers A, Yildiz FH, Sandkvist M (2014) The Type II secretion system delivers matrix proteins for biofilm formation by Vibrio cholerae. J Bacteriol 196(24):4245–4252. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Sandkvist M, Michel LO, Hough LP, Morales VM, Bagdasarian M, Koomey M, DiRita VJ, Bagdasarian M (1997) General secretion pathway (eps) genes required for toxin secretion and outer membrane biogenesis in Vibrio cholerae. J Bacteriol 179(22):6994–7003CrossRefGoogle Scholar
  65. 65.
    Sloup RE, Konal AE, Severin GB, Korir ML, Bagdasarian MM, Bagdasarian M, Waters CM (2017) Cyclic di-GMP and VpsR induce the expression of type II secretion in Vibrio cholerae. J Bacteriol 199(19).
  66. 66.
    Karran P, Lindahl T, Ofsteng I, Evensen GB, Seeberg E (1980) Escherichia coli mutants deficient in 3-methyladenine-DNA glycosylase. J Mol Biol 140(1):101–127CrossRefGoogle Scholar
  67. 67.
    Fernandez NL, Srivastava D, Ngouajio AL, Waters CM (2018) Cyclic di-GMP positively regulates DNA repair in Vibrio cholerae. J Bacteriol 200(15).
  68. 68.
    Kovacikova G, Lin W, Skorupski K (2005) Dual regulation of genes involved in acetoin biosynthesis and motility/biofilm formation by the virulence activator AphA and the acetate-responsive LysR-type regulator AlsR in Vibrio cholerae. Mol Microbiol 57(2):420–433. CrossRefPubMedGoogle Scholar
  69. 69.
    Tabor CW, Tabor H (1984) Polyamines. Annu Rev Biochem 53:749–790. CrossRefPubMedGoogle Scholar
  70. 70.
    McGinnis MW, Parker ZM, Walter NE, Rutkovsky AC, Cartaya-Marin C, Karatan E (2009) Spermidine regulates Vibrio cholerae biofilm formation via transport and signaling pathways. FEMS Microbiol Lett 299(2):166–174. CrossRefPubMedGoogle Scholar
  71. 71.
    Karatan E, Duncan TR, Watnick PI (2005) NspS, a predicted polyamine sensor, mediates activation of Vibrio cholerae biofilm formation by norspermidine. J Bacteriol 187(21):7434–7443. CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Sobe RC, Bond WG, Wotanis CK, Zayner JP, Burriss MA, Fernandez N, Bruger EL, Waters CM, Neufeld HS, Karatan E (2017) Spermine inhibits Vibrio cholerae biofilm formation through the NspS-MbaA polyamine signaling system. J Biol Chem 292(41):17025–17036. CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Hamana K (1997) Polyamine distribution patterns within the families Aeromonadaceae, Vibrionaceae, Pasteurellaceae, and Halomonadaceae, and related genera of the gamma subclass of the Proteobacteria. J Gen Appl Microbiol 43(1):49–59CrossRefGoogle Scholar
  74. 74.
    Hamana K, Matsuzaki S (1982) Widespread occurrence of norspermidine and norspermine in eukaryotic algae. J Biochem 91(4):1321–1328CrossRefGoogle Scholar
  75. 75.
    Michael AJ (2016) Polyamines in eukaryotes, bacteria, and archaea. J Biol Chem 291(29):14896–14903. CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Kibe R, Kurihara S, Sakai Y, Suzuki H, Ooga T, Sawaki E, Muramatsu K, Nakamura A, Yamashita A, Kitada Y, Kakeyama M, Benno Y, Matsumoto M (2014) Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice. Sci Rep 4:4548. CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Osborne DL, Seidel ER (1990) Gastrointestinal luminal polyamines: cellular accumulation and enterohepatic circulation. Am J Phys 258(4 Pt 1):G576–G584. CrossRefGoogle Scholar
  78. 78.
    Pegg AE (2016) Functions of polyamines in mammals. J Biol Chem 291(29):14904–14912. CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Cockerell SR, Rutkovsky AC, Zayner JP, Cooper RE, Porter LR, Pendergraft SS, Parker ZM, McGinnis MW, Karatan E (2014) Vibrio cholerae NspS, a homologue of ABC-type periplasmic solute binding proteins, facilitates transduction of polyamine signals independent of their transport. Microbiology 160(Pt 5):832–843. CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Schaller RA, Ali SK, Klose KE, Kurtz DM Jr (2012) A bacterial hemerythrin domain regulates the activity of a Vibrio cholerae diguanylate cyclase. Biochemistry 51(43):8563–8570. CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Townsley L, Sison Mangus MP, Mehic S, Yildiz FH (2016) Response of Vibrio cholerae to low-temperature shifts: CspV regulation of type VI secretion, biofilm formation, and association with zooplankton. Appl Environ Microbiol 82(14):4441–4452. CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Hung DT, Zhu J, Sturtevant D, Mekalanos JJ (2006) Bile acids stimulate biofilm formation in Vibrio cholerae. Mol Microbiol 59(1):193–201. CrossRefPubMedGoogle Scholar
  83. 83.
    Koestler BJ, Waters CM (2014) Bile acids and bicarbonate inversely regulate intracellular cyclic di-GMP in Vibrio cholerae. Infect Immun 82(7):3002–3014. CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Pratt JT, McDonough E, Camilli A (2009) PhoB regulates motility, biofilms, and cyclic di-GMP in Vibrio cholerae. J Bacteriol 191(21):6632–6642. CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Hammer BK, Bassler BL (2009) Distinct sensory pathways in Vibrio cholerae El Tor and classical biotypes modulate cyclic dimeric GMP levels to control biofilm formation. J Bacteriol 191(1):169–177. CrossRefGoogle Scholar
  86. 86.
    Waters CM, Lu W, Rabinowitz JD, Bassler BL (2008) Quorum sensing controls biofilm formation in Vibrio cholerae through modulation of cyclic di-GMP levels and repression of vpsT. J Bacteriol 190(7):2527–2536. CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Miller MB, Skorupski K, Lenz DH, Taylor RK, Bassler BL (2002) Parallel quorum sensing systems converge to regulate virulence in Vibrio cholerae. Cell 110(3):303–314CrossRefGoogle Scholar
  88. 88.
    Lenz DH, Mok KC, Lilley BN, Kulkarni RV, Wingreen NS, Bassler BL (2004) The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae. Cell 118(1):69–82. CrossRefPubMedGoogle Scholar
  89. 89.
    Hammer BK, Bassler BL (2007) Regulatory small RNAs circumvent the conventional quorum sensing pathway in pandemic Vibrio cholerae. Proc Natl Acad Sci USA 104(27):11145–11149. CrossRefPubMedGoogle Scholar
  90. 90.
    Zhao X, Koestler BJ, Waters CM, Hammer BK (2013) Post-transcriptional activation of a diguanylate cyclase by quorum sensing small RNAs promotes biofilm formation in Vibrio cholerae. Mol Microbiol 89(5):989–1002. CrossRefPubMedGoogle Scholar
  91. 91.
    Joelsson A, Liu Z, Zhu J (2006) Genetic and phenotypic diversity of quorum-sensing systems in clinical and environmental isolates of Vibrio cholerae. Infect Immun 74(2):1141–1147. CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Dahlstrom KM, Collins AJ, Doing G, Taroni JN, Gauvin TJ, Greene CS, Hogan DA, O’Toole GA (2018) A multimodal strategy used by a large c-di-GMP network. J Bacteriol 200(8).
  93. 93.
    Liu Z, Wang Y, Liu S, Sheng Y, Rueggeberg KG, Wang H, Li J, Gu FX, Zhong Z, Kan B, Zhu J (2015) Vibrio cholerae represses polysaccharide synthesis to promote motility in mucosa. Infect Immun 83(3):1114–1121. CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Ymele-Leki P, Houot L, Watnick PI (2013) Mannitol and the mannitol-specific enzyme IIB subunit activate Vibrio cholerae biofilm formation. Appl Environ Microbiol 79(15):4675–4683. CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Massie JP, Reynolds EL, Koestler BJ, Cong JP, Agostoni M, Waters CM (2012) Quantification of high-specificity cyclic diguanylate signaling. Proc Natl Acad Sci USA 109(31):12746–12751. CrossRefPubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Department of BiologyAppalachian State UniversityBooneUSA

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