Proteolysis of Virulence Regulator ToxR Is Associated with Entry of into a Dormant State

1. Huq A, Small EB, West PA, Huq MI, Rahman R, et al. (1983) Ecological relationships between Vibrio cholerae and planktonic crustacean copepods. Appl Environ Microbiol 45: 275–283. 6337551

2. Tamplin ML, Gauzens AL, Huq A, Sack DA, Colwell RR (1990) Attachment of Vibrio cholerae serogroup O1 to zooplankton and phytoplankton of Bangladesh waters. Appl Environ Microbiol 56: 1977–1980. 2383016

3. Almagro-Moreno S, Taylor RK (2013) Cholera: Environmental Reservoirs and Impact on Disease Transmission. Microbiol Spectrum 1(2):OH-0003-2012.

4. Lutz C, Erken M, Noorian P, Sun S, McDougald D (2013) Environmental reservoirs and mechanisms of persistence of Vibrio cholerae. Front Microbiol 4: 375. doi: 10.3389/fmicb.2013.00375 24379807

5. Taylor RK, Miller VL, Furlong DB, Mekalanos JJ (1987) Use of phoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin. Proc Natl Acad Sci USA 84: 2833–2837. 2883655

6. Sanchez J, Holmgren J (2008) Cholera toxin structure, gene regulation and pathophysiological and immunological aspects. Cell Mol Life Sci 65: 1347–1360. doi: 10.1007/s00018-008-7496-5 18278577

7. Matson JS, Withey JH, DiRita VJ (2007) Regulatory networks controlling Vibrio cholerae virulence gene expression. Infect Immun 75: 5542–5549. 17875629

8. Karaolis DK, Johnson JA, Bailey CC, Boedeker EC, Kaper JB, et al. (1998) A Vibrio cholerae pathogenicity island associated with epidemic and pandemic strains. Proc Natl Acad Sci USA 95: 3134–3139. 9501228

9. Miller VL, Taylor RK, Mekalanos JJ (1987) Cholera toxin transcriptional activator toxR is a transmembrane DNA binding protein. Cell 48: 271–279. 3802195

10. Carroll PA, Tashima KT, Rogers MB, DiRita VJ, Calderwood SB (1997) Phase variation in tcpH modulates expression of the ToxR regulon in Vibrio cholerae. Mol Microbiol 25: 1099–1111. 9350866

11. Häse CC, Mekalanos JJ (1998) TcpP protein is a positive regulator of virulence gene expression in Vibrio cholerae. Proc Natl Acad Sci USA 95: 730–734. 9435261

12. 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: 67–84. 11029691

13. DiRita VJ, Mekalanos JJ (1991) Periplasmic interaction between two membrane regulatory proteins, ToxR and ToxS, results in signal transduction and transcriptional activation. Cell 64: 29–37. 1898871

14. Champion GA, Neely MN, Brennan MA, DiRita VJ (1997) A branch in the ToxR regulatory cascade of Vibrio cholerae revealed by characterization of toxT mutant strains. Mol Microbiol 23: 323–331. 9044266

15. Merrell DS, Butler SM, Qadri F, Dolganov NA, Alam A, et al. (2002) Host-induced epidemic spread of the cholera bacterium. Nature 417: 642–645. 12050664

16. LaRocque RC, Harris JB, Dziejman M, Li X, Khan AI, et al. (2005) Transcriptional profiling of Vibrio cholerae recovered directly from patient specimens during early and late stages of human infection. Infect Immun 73: 4488–4493. 16040959

17. Abuaita BH, Withey JH (2011) Termination of Vibrio cholerae virulence gene expression is mediated by proteolysis of the major virulence activator, ToxT. Mol Microbiol 81: 1640–1653. doi: 10.1111/j.1365-2958.2011.07798.x 21883522

18. Matson JS, DiRita VJ (2005) Degradation of the membrane-localized virulence activator TcpP by the YaeL protease in Vibrio cholerae. Proc Natl Acad Sci USA 102: 16403–16408. 16254052

19. Urban S (2009) Making the cut: central roles of intramembrane proteolysis in pathogenic microorganisms. Nat Rev Microbiol 7: 411–423. doi: 10.1038/nrmicro2130 19421188

20. Heinrich J, Wiegert T (2009) Regulated intramembrane proteolysis in the control of extracytoplasmic function sigma factors. Res Microbiol 160: 696–703. doi: 10.1016/j.resmic.2009.08.019 19778605

21. Makinoshima H, Glickman MS (2005) Regulation of Mycobacterium tuberculosis cell envelope composition and virulence by intramembrane proteolysis. Nature 436: 406–409. 16034419

22. Alba BM, Gross CA (2004) Regulation of the Escherichia coli sigma-dependent envelope stress response. Mol Microbiol 52: 613–619. 15101969

23. Ades SE (2008) Regulation by destruction: design of the sigmaE envelope stress response. Curr Opin Microbiol 11: 535–540. doi: 10.1016/j.mib.2008.10.004 18983936

24. Ades SE, Connolly LE, Alba BM, Gross CA (1999) The Escherichia coli sigma(E)-dependent extracytoplasmic stress response is controlled by the regulated proteolysis of an anti-sigma factor. Genes Dev 13: 2449–2461. 10500101

25. Kanehara K, Ito K, Akiyama Y (2002) YaeL (EcfE) activates the sigma(E) pathway of stress response through a site-2 cleavage of anti-sigma(E), RseA. Genes Dev 16: 2147–2155. 12183368

26. Alba BM, Leeds JA, Onufryk C, Lu CZ, Gross CA (2002) DegS and YaeL participate sequentially in the cleavage of RseA to activate the sigma(E)-dependent extracytoplasmic stress response. Genes Dev 16: 2156–2168. 12183369

27. Schild S, Tamayo R, Nelson EJ, Qadri F, Calderwood SB, et al. (2007) Genes induced late in infection increase fitness of Vibrio cholerae after release into the environment. Cell Host Microbe 2: 264–277. 18005744

28. Nielsen AT, Dolganov NA, Otto G, Miller MC, Wu CY, et al. (2006) RpoS controls the Vibrio cholerae mucosal escape response. PLoS Pathog 2: e109. 17054394

29. Kamp HD, Patimalla-Dipali B, Lazinski DW, Wallace-Gadsden F, Camilli A (2013) Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle. PLoS Pathog 9: e1003800. doi: 10.1371/journal.ppat.1003800 24385900

30. Alam M, Sultana M, Nair GB, Siddique AK, Hasan NA, et al. (2007) Viable but nonculturable Vibrio cholerae O1 in biofilms in the aquatic environment and their role in cholera transmission. Proc Natl Acad Sci USA 104: 17801–17806. 17968017

31. Kamruzzaman M, Udden SMN, Cameron DE, Calderwood SB, Nair GB, et al. (2010) Quorum-regulated biofilms enhance the development of conditionally viable, environmental Vibrio cholerae. Proc Natl Acad Sci USA 107: 1588–1593. doi: 10.1073/pnas.0913404107 20080633

32. Faruque SM, Islam MJ, Ahmad QS, Biswas K, Faruque ASG, et al. (2006) An improved technique for isolation of environmental Vibrio cholerae with epidemic potential: monitoring the emergence of a multiple-antibiotic-resistant epidemic strain in Bangladesh. J Infect Dis 193: 1029–1036. 16518766

33. Xu HS, Roberts N, Singleton FL, Attwell RW, Grimes DJ, et al. (1982) Survival and viability of nonculturable Escherichia coli and Vibrio cholerae in the estuarine and marine environment. Microb Ecol 8: 313–323. doi: 10.1007/BF02010671 24226049

34. Bari SMN, Roky MK, Mohiuddin M, Kamruzzaman M, Mekalanos JJ, et al. (2013) Quorum-sensing autoinducers resuscitate dormant Vibrio cholerae in environmental water samples. Proc Natl Acad Sci USA 110: 9926–9931. doi: 10.1073/pnas.1307697110 23716683

35. Bina J, Zhu J, Dziejman M, Faruque S, Calderwood S, et al. (2003) ToxR regulon of Vibrio cholerae and its expression in vibrios shed by cholera patients. Proc Natl Acad Sci USA 100: 2801–2806. 12601157

36. Miller VL, Mekalanos JJ (1988) A novel suicide vector and its use in construction of insertion mutations: osmoregulation of outer membrane proteins and virulence determinants in Vibrio cholerae requires toxR. J Bacteriol 170: 2575–2583. 2836362

37. Li CC, Merrell DS, Camilli A, Kaper JB (2002) ToxR interferes with CRP-dependent transcriptional activation of ompT in Vibrio cholerae. Mol Microbiol 43: 1577–1589. 11952906

38. Mey AR, Craig SA, Payne SM (2011) The effects of amino acid supplementation on porin expression and ToxR levels in Vibrio cholerae. Infect Immun. 80: 518–528. doi: 10.1128/IAI.05851-11 22144480

39. Medrano AI, DiRita VJ, Castillo G, Sanchez J (1999) Transient transcriptional activation of the Vibrio cholerae El Tor virulence regulator toxT in response to culture conditions. Infect Immun 67: 2178–2183. 10225872

40. DiRita VJ, Neely M, Taylor RK, Bruss PM (1996) Differential expression of the ToxR regulon in classical and E1 Tor biotypes of Vibrio cholerae is due to biotype-specific control over toxT expression. Proc Natl Acad Sci USA 93: 7991–7995. 8755590

41. LaRocque RC, Krastins B, Harris JB, Lebrun LM, Parker KC, et al. (2008) Proteomic analysis of Vibrio cholerae in human stool. Infect Immun 76: 4145–4151. doi: 10.1128/IAI.00585-08 18591230

42. Kirn TJ, Jude BA, Taylor RK (2005) A colonization factor links Vibrio cholerae environmental survival and human infection. Nature 438: 863–866. 16341015

43. Mathur J, Davis BM, Waldor MK (2007) Antimicrobial peptides activate the Vibrio cholerae sigmaE regulon through an OmpU-dependent signalling pathway. Mol Microbiol 63: 848–858. 17181782

44. Kovacikova G, Skorupski K (2002) The alternative sigma factor sigma(E) plays an important role in intestinal survival and virulence in Vibrio cholerae. Infect Immun 70: 5355–5362. 12228259

45. Raivio TL, Silhavy TJ (1999) The sigmaE and Cpx regulatory pathways: overlapping but distinct envelope stress responses. Curr Opin Microbiol 2: 159–165. 10322173

46. Ruiz N, Silhavy TJ (2005) Sensing external stress: watchdogs of the Escherichia coli cell envelope. Curr Opin Microbiol 8: 122–126. 15802241

47. Slamti L, Waldor MK (2009) Genetic analysis of activation of the Vibrio cholerae Cpx pathway. J Bacteriol 191: 5044–5056. doi: 10.1128/JB.00406-09 19542291

48. Kirn TJ, Lafferty MJ, Sandoe CM, Taylor RK (2000) Delineation of pilin domains required for bacterial association into microcolonies and intestinal colonization by Vibrio cholerae. Mol Microbiol 35: 896–910. 10692166

49. Wai SN, Mizunoe Y, Yoshida S (1999) How Vibrio cholerae survive during starvation. FEMS Microbiology Letters 180: 123–131. 10556702

50. Pruzzo C, Tarsi R, Lleò MM, Signoretto C, Zampini M, et al. (2003) Persistence of adhesive properties in Vibrio cholerae after long-term exposure to sea water. Environ Microbiol 5: 850–858. 14510838

51. Gonzalez-Escalona N, Fey A, Höfle MG, Espejo RT, A Guzmán C (2006) Quantitative reverse transcription polymerase chain reaction analysis of Vibrio cholerae cells entering the viable but non-culturable state and starvation in response to cold shock. Environ Microbiol 8: 658–666. 16584477

52. Crawford JA, Krukonis ES, DiRita VJ (2003) Membrane localization of the ToxR winged-helix domain is required for TcpP-mediated virulence gene activation in Vibrio cholerae. Mol Microbiol 47: 1459–1473. 12603748

53. Chaiyanan S, Chaiyanan S, Grim C, Maugel T, Huq A, et al. (2007) Ultrastructure of coccoid viable but non-culturable Vibrio cholerae. Environ Microbiol 9: 393–402. 17222137

54. Krebs SJ, Taylor RK (2011) Nutrient-dependent, rapid transition of Vibrio cholerae to coccoid morphology and expression of the toxin co-regulated pilus in this form. Microbiol 157: 2942–2953. doi: 10.1099/mic.0.048561-0 21778208

55. Pradhan S, Mallick SK, Chowdhury R (2013) Vibrio cholerae classical biotype is converted to the viable non-culturable state when cultured with the El Tor biotype. PLoS ONE 8: e53504. doi: 10.1371/journal.pone.0053504 23326443

56. Whitaker WB, Parent MA, Boyd A, Richards GP, Boyd EF (2012) The Vibrio parahaemolyticus ToxRS Regulator Is Required for Stress Tolerance and Colonization in a Novel Orogastric Streptomycin-Induced Adult Murine Model. Infect Immun 80: 1834–1845. doi: 10.1128/IAI.06284-11 22392925

57. Wong HC, Wang P (2004) Induction of viable but nonculturable state in Vibrio parahaemolyticus and its susceptibility to environmental stresses. J Appl Microbiol 96: 359–366. 14723697

58. Merrell DS, Bailey C, Kaper JB, Camilli A (2001) The ToxR-mediated organic acid tolerance response of Vibrio cholerae requires OmpU. J Bacteriol 183: 2746–2754. 11292792

59. Rudner DZ, Fawcett P, Losick R (1999) A family of membrane-embedded metalloproteases involved in regulated proteolysis of membrane-associated transcription factors. Proc Natl Acad Sci USA 96: 14765–14770. 10611287

60. Bramkamp M, Weston L, Daniel RA, Errington J (2006) Regulated intramembrane proteolysis of FtsL protein and the control of cell division in Bacillus subtilis. Mol Microbiol 62: 580–591. 17020588

61. An FY, Sulavik MC, Clewell DB (1999) Identification and characterization of a determinant (eep) on the Enterococcus faecalis chromosome that is involved in production of the peptide sex pheromone cAD1. J Bacteriol 181: 5915–5921. 10498702

62. Stevenson LG, Strisovsky K, Clemmer KM, Bhatt S, Freeman M, et al. (2007) Rhomboid protease AarA mediates quorum-sensing in Providencia stuartii by activating TatA of the twin-arginine translocase. Proc Natl Acad Sci USA 104: 1003–1008. 17215357

63. Heinrich J, Lundén T, Kontinen VP, Wiegert T (2008) The Bacillus subtilis ABC transporter EcsAB influences intramembrane proteolysis through RasP. Microbiol 154: 1989–1997.

64. Qiu D, Eisinger VM, Rowen DW, Yu HD (2007) Regulated proteolysis controls mucoid conversion in Pseudomonas aeruginosa. Proc Natl Acad Sci USA 104: 8107–8112. 17470813

65. Rattanama P, Thompson JR, Kongkerd N, Srinitiwarawong K, Vuddhakul V, et al. (2012) Sigma E Regulators Control Hemolytic Activity and Virulence in a Shrimp Pathogenic Vibrio harveyi. PLoS ONE 7: e32523. doi: 10.1371/journal.pone.0032523 22384269

66. Chatterjee E, Chowdhury R (2013) Reduced virulence of the Vibrio cholerae fadD mutant is due to induction of the extracytoplasmic stress response. Infect Immun 81: 3935–3941. doi: 10.1128/IAI.00722-13 23918781

67. Haines-Menges B, Whitaker WB, Boyd EF (2014) The alternative sigma factor RpoE is important for Vibrio parahaemolyticus cell envelope stress response and intestinal colonization. Infect Immun 89: 3667–3677.

68. Palonen E, Lindström M, Somervuo P, Korkeala H (2013) Alternative sigma factor σE has an important role in stress tolerance of Yersinia pseudotuberculosis IP32953. Appl Environ Microbiol 79: 5970–5977. doi: 10.1128/AEM.01891-13 23872565

69. Pfau JD, Taylor RK (1998) Mutations in toxR and toxS that separate transcriptional activation from DNA binding at the cholera toxin gene promoter. J Bacteriol 180: 4724. 9721317

70. Ding Y, Davis BM, Waldor MK (2004) Hfq is essential for Vibrio cholerae virulence and downregulates sigma expression. Mol Microbiol 53: 345–354. 15225327

71. Colwell R (2009) Viable but Not Cultivable Bacteria. In: Epstein SS, editor. Microbiology Monographs. Springer Berlin Heidelberg, 10: 121–129.

72. Oliver JD (2010) Recent findings on the viable but nonculturable state in pathogenic bacteria. FEMS Microbiol Rev 34: 415–425. doi: 10.1111/j.1574-6976.2009.00200.x 20059548

73. Ravel J, Knight IT, Monahan CE, Hill RT, Colwell RR (1995) Temperature-induced recovery of Vibrio cholerae from the viable but nonculturable state: growth or resuscitation?. Microbiol 141: 377–383.

74. Thomas KU, Joseph N, Raveendran O, Nair S (2006) Salinity-induced survival strategy of Vibrio cholerae associated with copepods in Cochin backwaters. Mar Pollut Bull 52: 1425–1430. 16764894

75. Reich KA, Schoolnik GK (1994) The light organ symbiont Vibrio fischeri possesses a homolog of the Vibrio cholerae transmembrane transcriptional activator ToxR. J Bacteriol 176: 3085–3088. 8188612

76. Lee SE, Shin SH, Kim SY, Kim YR, Shin DH, et al. (2000) Vibrio vulnificus has the transmembrane transcription activator ToxRS stimulating the expression of the hemolysin gene vvhA. J Bacteriol 182: 3405–3415. 10852871

77. Montieri S, Suffredini E, Ciccozzi M, Croci L (2010) Phylogenetic and evolutionary analysis of Vibrio parahaemolyticus and Vibrio alginolyticus isolates based on toxR gene sequence. New Microbiol 33: 359–372. 21213595

78. Ruwandeepika HAD, Defoirdt T, Bhowmick PP, Shekar M, Bossier P, et al. (2010) Presence of typical and atypical virulence genes in Vibrio isolates belonging to the Harveyi clade. J Appl Microbiol 109: 888–899. doi: 10.1111/j.1365-2672.2010.04715.x 20345385

79. Welch TJ, Bartlett DH (1998) Identification of a regulatory protein required for pressure-responsive gene expression in the deep-sea bacterium Photobacterium species strain SS9. Mol Microbiol 27: 977–985. 9535087

80. Bartlett D, Chi E (1994) Genetic characterization of ompH mutants in the deep-sea bacterium Photobacterium sp. strain SS9. Arch Microbiol 162: 323–328. 7857197

81. Chi E, Bartlett DH (1995) An rpoE-like locus controls outer membrane protein synthesis and growth at cold temperatures and high pressures in the deep-sea bacterium Photobacterium sp. strain SS9. Mol Microbiol 17: 713–726. 8801425

82. Patnaik BK, Ghosh HK (1966) Histopathological studies on experimental cholera. Br J Exp Pathol 47: 210–214.

83. de Lorenzo V, Timmis KN (1994) Analysis and construction of stable phenotypes in gram-negative bacteria with Tn5- and Tn10-derived minitransposons. Meth Enzymol 235: 386–405. 8057911

84. Skorupski K, Taylor RK (1996) Positive selection vectors for allelic exchange. Gene 169: 47–52. 8635748

85. Nye MB, Pfau JD, Skorupski K, Taylor RK (2000) Vibrio cholerae H-NS silences virulence gene expression at multiple steps in the ToxR regulatory cascade. J Bacteriol 182: 4295–4303. 10894740