1887

Chapter 20 : Role of Cyclic Di-GMP in Virulence

Authors: Jason T. Pratt1, Rita Tamayo2, Andrew Camilli3
VIEW AFFILIATIONS HIDE AFFILIATIONS
Affiliations: 1: Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111; 2: Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; 3: Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111
Content Type: Monograph
Publication Year: 2010

Category: Microbial Genetics and Molecular Biology

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Preview Magnify
Zoom in
Zoomout

Role of Cyclic Di-GMP in Virulence, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816667/9781555814991_Chap20-1.gif /docserver/preview/fulltext/10.1128/9781555816667/9781555814991_Chap20-2.gif

Abstract:

The bacterial allosteric regulator and secondary messenger cyclic di-GMP (c-di-GMP) plays an integral role in the life cycle of pathogenic by helping to mediate the environment-to-host transition. The regulation of the intracellular concentration of c-di-GMP in is complex, as there is an abundance of genes coding for diguanylate cyclases (DGCs) and phosphodiesterase (PDEs). This chapter focuses on the role of c-di-GMP in the regulation of virulence mechanisms during colonization and dissemination. The two most important virulence factors expressed by are cholera toxin (CT) and the toxin-coregulated pilus (TCP). In vitro expression studies have shown that c-di-GMP has a negative effect on virulence gene expression, specifically CT. Although motility has been well studied, the role of motility in pathogenesis remains unclear. There is an abundance of information regarding physiological behaviors regulated by c-di-GMP, but relatively little is known about the mechanism(s) of this regulation. It is understood that the intracellular concentration of c-di-GMP is modulated by the enzymatic activities of DGCs and PDEs, but it is not known how these changes in concentration signal for the vast alterations in bacterial behavior are observed. Identification of new regulatory pathways will provide new insight into the cdi-GMP regulatory circuit and will help to explain how this secondary messenger molecule is so important to pathogenesis and environmental fitness.

Citation: Pratt J, Tamayo R, Camilli A. 2010. Role of Cyclic Di-GMP in Virulence, p 293-303. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch20

Key Concept Ranking

Enzyme-Linked Immunosorbent Assay
0.43624917
0.43624917
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Role of Cyclic Di-GMP in Vibrio cholerae Virulence
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555816667.ch20-1,webId=/content/author/10.1128/9781555816667.ch20-1,properties={foaf_givenname=Jason T., foaf_name=Jason T. Pratt, foaf_surname=Pratt, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555816667.ch20-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555816667.ch20-2,webId=/content/author/10.1128/9781555816667.ch20-2,properties={foaf_givenname=Rita, foaf_name=Rita Tamayo, foaf_surname=Tamayo, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555816667.ch20-aff2]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555816667.ch20-3,webId=/content/author/10.1128/9781555816667.ch20-3,properties={foaf_givenname=Andrew, foaf_name=Andrew Camilli, foaf_surname=Camilli, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555816667.ch20-aff3]]}]]
Citation: Pratt J, Tamayo R, Camilli A. 2010. Role of Cyclic Di-GMP in Virulence, p 293-303. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch20
/content/10.1128/9781555816667.ch20.ch20fig01
Figure 1.
The ToxR regulon in is repressed by c-di-GMP. Arrows indicate activation of genes or proteins; parallel lines in place of an arrowhead represent repression. The predicted interaction of c-di-GMP with the regulon is shown. High c-di-GMP concentration results in decreased transcription, consequently causing reduced expression and CT production. c-di-GMP may also regulate ToxT activity, because gene expression is unaffected by high c-di-GMP. CRP, cAMP receptor protein.
10.1128/9781555816667/f0295-01_thmb.gif
10.1128/9781555816667/f0295-01.gif
Image of Figure 1.
Figure 1.

The ToxR regulon in is repressed by c-di-GMP. Arrows indicate activation of genes or proteins; parallel lines in place of an arrowhead represent repression. The predicted interaction of c-di-GMP with the regulon is shown. High c-di-GMP concentration results in decreased transcription, consequently causing reduced expression and CT production. c-di-GMP may also regulate ToxT activity, because gene expression is unaffected by high c-di-GMP. CRP, cAMP receptor protein.

Citation: Pratt J, Tamayo R, Camilli A. 2010. Role of Cyclic Di-GMP in Virulence, p 293-303. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch20
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555816667.ch20.ch20fig02
Figure 2.
RIVET. RIVET was used to examine the expression of genes during infection of the infant mouse. Transcriptional fusions of which encodes a resolvase, to promoters of interest (here, P) are made. When a promoter is activated in response to undefined signals present in the host, TnpR is produced and targets sites (indicated by grey rectangles). The sites flank (kanamycin resistance) and (sucrose sensitivity) genes, and recognition by TnpR results in excision, or resolution, of Thus, loss of kanamycin resistance and sucrose sensitivity represents expression of the gene of interest in a given condition ( ). RIVET was used to show that c-di-GMP concentration is decreased upon infection to allow maximal virulence gene expression ( ). In addition, a modified RIVET was used to identify genes expressed late during infection, including three GGDEF genes and one GGDEF-EAL hybrid.
10.1128/9781555816667/f0296-01_thmb.gif
10.1128/9781555816667/f0296-01.gif
Image of Figure 2.
Figure 2.

RIVET. RIVET was used to examine the expression of genes during infection of the infant mouse. Transcriptional fusions of which encodes a resolvase, to promoters of interest (here, P) are made. When a promoter is activated in response to undefined signals present in the host, TnpR is produced and targets sites (indicated by grey rectangles). The sites flank (kanamycin resistance) and (sucrose sensitivity) genes, and recognition by TnpR results in excision, or resolution, of Thus, loss of kanamycin resistance and sucrose sensitivity represents expression of the gene of interest in a given condition ( ). RIVET was used to show that c-di-GMP concentration is decreased upon infection to allow maximal virulence gene expression ( ). In addition, a modified RIVET was used to identify genes expressed late during infection, including three GGDEF genes and one GGDEF-EAL hybrid.

Citation: Pratt J, Tamayo R, Camilli A. 2010. Role of Cyclic Di-GMP in Virulence, p 293-303. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch20
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555816667.ch20.ch20fig03
Figure 3.
c-di-GMP regulates motility gene expression in Schematic of motility gene hierarchy, represented by the function of genes within each class. Classes are denoted by roman numerals I to IV. Gene regulators or proteins of note are named. Arrows indicate activation of genes, and parallel lines in place of an arrowhead indicate gene repression. Transcriptional profiling studies have shown that c-di-GMP represses the expression of all class III and IV genes and some class II genes, including FliA, which is required for expression of class IV genes. Despite this information, there is no model to account for the effects of c-di-GMP on motility at this time.
10.1128/9781555816667/f0298-01_thmb.gif
10.1128/9781555816667/f0298-01.gif
Image of Figure 3.
Figure 3.

c-di-GMP regulates motility gene expression in Schematic of motility gene hierarchy, represented by the function of genes within each class. Classes are denoted by roman numerals I to IV. Gene regulators or proteins of note are named. Arrows indicate activation of genes, and parallel lines in place of an arrowhead indicate gene repression. Transcriptional profiling studies have shown that c-di-GMP represses the expression of all class III and IV genes and some class II genes, including FliA, which is required for expression of class IV genes. Despite this information, there is no model to account for the effects of c-di-GMP on motility at this time.

Citation: Pratt J, Tamayo R, Camilli A. 2010. Role of Cyclic Di-GMP in Virulence, p 293-303. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch20
Permissions and Reprints Request Permissions
Download as Powerpoint
/content/10.1128/9781555816667.ch20.ch20fig04
Figure 4.
The intracellular concentration of c-di-GMP fluctuates throughout the life cycle of The solid line indicates the relative level of intracellular c-di-GMP, which is predicted to oscillate as shifts from aquatic reservoirs (ex vivo) to the host small intestine (in vivo) and back again; dashed lines demarcate these transition points. c-di-GMP is predicted to be high in the aquatic environment and in the biofilm state. The induction of PDEs upon entry into the host and the negative effect of c-di-GMP, in vitro and in vivo, on virulence gene expression suggest that c-di-GMP must be lowered upon infection. When is disseminated from the host, c-di-GMP must be elevated again to aid survival in the environment. Evidence suggests that elevation of c-di-GMP by begins prior to exiting the host during advanced cholera, possibly in response to changing conditions in the intestine.
10.1128/9781555816667/f0301-01_thmb.gif
10.1128/9781555816667/f0301-01.gif
Image of Figure 4.
Figure 4.

The intracellular concentration of c-di-GMP fluctuates throughout the life cycle of The solid line indicates the relative level of intracellular c-di-GMP, which is predicted to oscillate as shifts from aquatic reservoirs (ex vivo) to the host small intestine (in vivo) and back again; dashed lines demarcate these transition points. c-di-GMP is predicted to be high in the aquatic environment and in the biofilm state. The induction of PDEs upon entry into the host and the negative effect of c-di-GMP, in vitro and in vivo, on virulence gene expression suggest that c-di-GMP must be lowered upon infection. When is disseminated from the host, c-di-GMP must be elevated again to aid survival in the environment. Evidence suggests that elevation of c-di-GMP by begins prior to exiting the host during advanced cholera, possibly in response to changing conditions in the intestine.

Citation: Pratt J, Tamayo R, Camilli A. 2010. Role of Cyclic Di-GMP in Virulence, p 293-303. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch20
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555816667.ch20
1. Amikam, D., and, M. Y. Galperin. 2006. PilZ domain is part of the bacterial c-di-GMP binding protein. Bioinformatics 22: 3– 6.
2. Ausmees, N.,, R. Mayer,, H. Weinhouse,, G. Volman,, D. Amikam,, M. Benziman, and, M. Lindberg. 2001. Genetic data indicate that proteins containing the GGDEF domain possess diguanylate cyclase activity. FEMS Microbiol. Lett. 204: 163– 167.
3. Banwell, J. G.,, N. F. Pierce,, R. C. Mitra,, K. L. Brigham,, G. J. Caranasos,, R. I. Keimowitz,, D. S. Fedson,, J. Thomas,, S. L. Gorbach,, R. B. Sack, and, A. J. Mondal. 1970. Intestinal fluid and electrolyte transport in human cholera. J. Clin Investig. 49: 183– 195.
4. Barua, D. 1991. History of cholera, p. 1-35. In D. Barua and, W. B. Greenough III (ed.), Cholera. Plenum Medical Book Company, New York, NY.
5. Beck, N. A.,, E. S. Krukonis, and, V. J. DiRita. 2004. TcpH influences virulence gene expression in Vibrio cholerae by inhibiting degradation of the transcription activator TcpP. J. Bacteriol. 186: 8309– 8316.
6. Benach, J.,, S. S. Swaminathan,, R. Tamayo,, S. K. Handelman,, E. Folta-Stogniew,, J. E. Ramos,, F. Forouhar,, H. Neely,, J. Seetharaman,, A. Camilli, and, J. F. Hunt. 2007. The structural basis of cyclic diguanylate signal transduction by PilZ domains. EMBO J. 26: 5153– 5166.
7. Bennish, M. L. 1994. Cholera: pathophysiology, clinical features, and treatment, p. 3-25. In K. Wachsmut,, P. A. Blake, and, O. Olsvik (ed.), Vibrio cholerae and Cholera: Molecular to Global Perspectives. ASM Press, Washington, DC.
8. Beyhan, S.,, A. D. Tischler,, A. Camilli, and, F. H. Yildiz. 2006. Differences in gene expression between the classical and El Tor biotypes of Vibrio cholerae O1. Infect. Immun. 74: 3633– 3642.
9. Beyhan, S.,, A. D. Tischler,, A. Camilli, and, F. H. Yildiz. 2006. Transcriptome and phenotypic responses of Vibrio cholerae to increased cyclic di-GMP level. J. Bacteriol. 188: 3600– 3613.
10. Bhowmick, R.,, A. Ghosal,, B. Das,, H. Koley,, D. R. Saha,, S. Ganguly,, R. K. Nandy,, R. K. Bhadra, and, N. S. Chatterjee. 2008. Intestinal adherence of Vibrio cholerae involves a coordinated interaction between colonization factor GbpA and mucin. Infect. Immun. 76: 4968– 4977.
11. Bobrov, A. G.,, O. Kirillina, and, R. D. Perry. 2005. The phosphodiesterase activity of the HmsP EAL domain is required for negative regulation of biofilm formation in Yersinia pestis. FEMS Microbiol. Lett. 247: 123– 130.
12. Breaker, R. R. 2008. Complex riboswitches. Science 319: 1795– 1797.
13. Butler, S. M., and, A. Camilli. 2004. Both chemotaxis and net motility greatly influence the infectivity of Vibrio cholerae. Proc. Natl. Acad. Sci. USA 101: 5018– 5023.
14. Butler, S. M.,, E. J. Nelson,, N. Chowdhury,, S. M. Faruque,, S. B. Calderwood, and, A. Camilli. 2006. Cholera stool bacteria repress chemotaxis to increase infectivity. Mol. Microbiol. 60: 417– 426.
15. Camilli, A., and, J. J. Mekalanos. 1995. Use of recombinase gene fusions to identify Vibrio cholerae genes induced during infection. Mol. Microbiol. 18: 671– 683.
16. Christen, B.,, M. Christen,, R. Paul,, F. Schmid,, M. Folcher,, P., Jenoe,, M. Meuwly, and, U. Jenal. 2006. Allosteric control of cyclic di-GMP signaling. J. Biol. Chem. 281: 32015– 32024.
17. Christen, M.,, B. Christen,, M. Folcher,, A. Schauerte, and, U. Jenal. 2005. Identification and characterization of a cyclic di-GMP-specific phosphodiesterase and its allosteric control byGTP. J. Biol. Chem. 280: 30829– 30837.
18. Crawford, J. A.,, E. S. Krukonis, and, V. J. DiRita. 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.
19. DiRita, V. J., and, J. J. Mekalanos. 1991. Periplasmic interaction between two membrane regulatory proteins, ToxR and ToxS, results in signal transduction and transcriptional activation. Cell 64: 29– 37.
20. DiRita, V. J.,, C. Parsot,, G. Jander, and, J. J. Mekalanos. 1991. Regulatory cascade controls virulence in Vibrio cholerae. Proc. Natl. Acad. Sci. USA 88: 5403– 5407.
21. Field, M. 1979. Mechanism of action of cholera and Escherichia coli toxins. Am. J. Clin. Nutr. 32: 189– 196.
22. Freter, R.,, P. C. O’Brien, and, M. S. Macsai. 1981. Role of chemotaxis in the association of motile bacteria with intestinal mucosa: in vivo studies. Infect. Immun. 34: 234– 240.
23. Galperin, M. Y.,, A. N. Nikolskaya, and, E. V. Koonin. 2001. Novel domains of the prokaryotic two-component signal transduction systems. FEMS Microbiol. Lett. 203: 11– 21.
24. Gill, D. M., and, C. A. King. 1975. The mechanism of action of cholera toxin in pigeon erythrocyte lysates. J. Biol. Chem. 250: 6424– 6432.
25. Guentzel, M. N.,, L. H. Field,, E. R. Eubanks, and, L. J. Berry. 1977. Use of fluorescent antibody in studies of immunity to cholera in infant mice. Infect. Immun. 15: 539– 548.
26. Gupta, S., and, R. Chowdhury. 1997. Bile affects production of virulence factors and motility of Vibrio cholerae. Infect. Immun. 65: 1131– 1134.
27. Herrington, D. A.,, R. H. Hall,, G. Losonsky,, J. J. Mekalanos,, R. K. Taylor, and, M. M. Levine. 1988. Toxin, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans. J. Exp. Med. 168: 1487– 1492.
28. Hickman, J. W., and, C. S. Harwood. 2008. Identification of FleQ from Pseudomonas aeruginosa as a c-di-GMP-responsive transcription factor. Mol. Microbiol. 69: 376– 389.
29. Higgins, D. E.,, E. Nazareno, and, V. J. DiRita. 1992. The virulence gene activator ToxT from Vibrio cholerae is a member of the AraC family of transcriptional activators. J. Bacteriol. 174: 6974– 6980.
30. Huq, A.,, E. B. Small,, P. A. West,, M. I. Huq,, R. Rahman, and, R. R. Colwell. 1983. Ecological relationships between Vibrio cholerae and planktonic crustacean copepods. Appl. Environ. Microbiol. 45: 275– 283.
31. Kaper, J. B.,, A. Rasano, and, M. Truskis. 1994. Toxins of Vibrio cholerae, p. 145-176. In K. Wachsmut,, P. A. Blake, and, O. Olsvik (ed.), Vibrio cholerae and Cholera: Molecular to Global Perspectives. ASM Press, Washington, DC.
32. Kaysner, C. A., and, W. E. Hill. 1994. Toxigenic Vibrio cholerae 01 in food and water, p. 27-40. In K. Wachsmut,, P. A. Blake, and, O. Olsvik (ed.), Vibrio cholerae and Cholera: Molecular to Global Perspectives. ASM Press, Washington, DC.
33. Kierek, K., and, P. I. Watnick. 2003. Environmental determinants of Vibrio cholerae biofilm development. Appl. Environ. Microbiol. 69: 5079– 5088.
34. King, C. A., and, W. A. van Heyningen. 1973. Deactivation of cholera toxin by a sialidase-resistant monosialosylganglioside. J. Infect. Dis. 127: 639– 647.
35. Kirn, T. J.,, M. J. Lafferty,, C. M. Sandoe, and, R. K. Taylor. 2000. Delineation of pilin domains required for bacterial association into microcolonies and intestinal colonization by Vibrio cholerae. Mol. Microbiol. 35: 896– 910.
36. Kirn, T. J.,, B. A. Jude, and, R. K. Taylor. 2005. A colonization factor links Vibrio cholerae environmental survival and human infection. Nature 438: 863– 866.
37. Kovacikova, G., and, K. Skorupski. 1999. A Vibrio cholerae LysR homolog, AphB, cooperates with AphA at the tcpPH promoter to activate expression of the ToxR virulence cascade. J. Bacteriol. 181: 4250– 4256.
38. Kovacikova, G., and, K. Skorupski. 2001. Overlapping binding sites for the virulence gene regulators AphA, AphB and cAMP-CRP at the Vibrio cholerae tcpPH promoter. Mol. Microbiol. 41: 393– 407.
39. Kovacikova, G., and, K. Skorupski. 2002. Regulation of virulence gene expression in Vibrio cholerae by quorum sensing: HapR functions at the aphA promoter. Mol. Microbiol. 46: 1135– 1147.
40. Krukonis, E. S.,, R. R. Yu, and, V. J. Dirita. 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.
41. Larocque, R. C.,, J. B. Harris,, M. Dziejman,, X. Li,, A. I. Khan,, A. S. Faruque,, S. M. Faruque,, G. B. Nair,, E. T. Ryan,, F. Qadri,, J. J. Mekalanos, and, S. B. Calderwood. 2005. Transcriptional profiling of Vibrio cholerae recovered directly from patient specimens during early and late stages of human infection. Infect. Immun. 73: 4488– 4493.
42. Lee, S. H.,, M. J. Angelichio,, J. J. Mekalanos, and, A. Camilli. 1998. Nucleotide sequence and spatiotemporal expression of the Vibrio cholerae vieSAB genes during infection. J. Bacteriol. 180: 2298– 2305.
43. Lee, S. H.,, S. M. Butler, and, A. Camilli. 2001. Selection for in vivo regulators of bacterial virulence. Proc. Natl. Acad. Sci.USA 98: 6889– 6894.
44. Lee, S. H.,, D. L. Hava,, M. K. Waldor, and, A. Camilli. 1999. Regulation and temporal expression patterns of Vibrio cholerae virulence genes during infection. Cell 99: 625– 634.
45. Lee, V. T.,, J. M. Matewish,, J. L. Kessler,, M. Hyodo,, Y. Hayakawa, and, S. Lory. 2007. A cyclic-di-GMP receptor required for bacterial exopolysaccharide production. Mol. Microbiol. 65: 1474– 1484.
46. Lim, B.,, S. Beyhan,, J. Meir, and, F. H. Yildiz. 2006. Cyclic-diGMP signal transduction systems in Vibrio cholerae: modulation of rugosity and biofilm formation. Mol. Microbiol. 60: 331– 348.
47. Martinez-Wilson,, H. F.,, R. Tamayo,, A. D. Tischler,, D. W. Lazinski, and, A. Camilli. 2008. The Vibrio cholerae hybrid sensor kinase VieS contributes to motility and biofilm regulation by altering the cyclic diguanylate level. J. Bacteriol. 190: 6439– 6447.
48. Matson, J. S., and, V. J. DiRita. 2005. Degradation of the membrane-localized virulence activator TcpP by the YaeL protease in Vibrio cholerae. Proc. Natl. Acad. Sci. USA 102: 16403– 16408.
49. Mekalanos, J. J.,, R. J. Collier, and, W. R. Romig. 1979. Enzymic activity of cholera toxin. I. New method of assay and the mechanism of ADP-ribosyl transfer. J. Biol. Chem. 254: 5849– 5854.
50. Merrell, D. S.,, S. M. Butler,, F. Qadri,, N. A. Dolganov,, A. Alam,, M. B. Cohen,, S. B. Calderwood,, G. K. Schoolnik, andCamilli. 2002. Host-induced epidemic spread of the cholera bacterium. Nature 417: 642– 645.
51. Miller, M. B.,, K. Skorupski,, D. H. Lenz,, R. K. Taylor, andL. Bassler. 2002. Parallel quorum sensing systems converge to regulate virulence in Vibrio cholerae. Cell 110: 303– 314.
52. Miller, V. L., and, J. J. Mekalanos. 1984. Synthesis of cholera toxin is positively regulated at the transcriptional level by toxR. Proc. Natl. Acad. Sci. USA 81: 3471– 3475.
53. Miller, V. L., and, J. J. Mekalanos. 1985. Genetic analysis of the cholera toxin-positive regulatory gene toxR. J. Bacteriol. 163: 580– 585.
54. Morris, J. G., Jr., and the Cholera Laboratory Task Force. 1994. Vibrio cholerae 0139 Bengal, p. 95-102. In K. Wachsmut,, P. A. Blake, and, O. Olsvik (ed.), Vibrio cholerae and Cholera: Molecular to Global Perspectives. ASM Press, Washington, DC.
55. Nelson, E. J.,, A. Chowdhury,, J. Flynn,, S. Schild,, L. Bourassa,, Y. Shao,, R. C. LaRocque,, S. B. Calderwood,, F. Qadri, and, A. Camilli. 2008. Transmission of Vibrio cholerae is antagonized by lytic phage and entry into the aquatic environment. PLoS Pathog. 4: e1000187.
56. Nielsen, A. T.,, N. A. Dolganov,, G. Otto,, M. C. Miller,, C. Y. Wu, and, G. K. Schoolnik. 2006. RpoS controls the Vibrio cholerae mucosal escape response. PLoS Pathog. 2: e109.
57. Paul, R.,, S. Weiser,, N. C. Amoit,, C. Chan,, T. Schirmer,, B. Giese, and, U. Jenal. 2004. Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel diguanylate cyclase output domain. Genes Dev. 18: 715– 727.
58. Pfau, J. D., and, R. K. Taylor. 1998. Mutations in toxR and toxS that separate transcriptional activation from DNA binding at the cholera toxin gene promoter. J. Bacteriol. 180: 4724– 4733.
59. Pierce, N. F. 1973. Differential inhibitory effects of cholera toxoids and ganglioside on the enterotoxin of Vibrio cholerae and Escherichia coli. J. Exp. Med. 137: 1009– 1023.
60. Postnova, T.,, O. G. Gómez-Duarte, and, K. Richardson. 1996. Motility mutants of Vibrio cholerae O1 have reduced adherence in vitro to human small intestinal epithelial cells as demonstrated by ELISA. Microbiology 142: 2767– 2776.
61. Pratt, J. T.,, R. Tamayo,, A. D. Tischler, and, A. Camilli. 2007. PilZ domain proteins bind cyclic diguanylate and regulate diverse processes in Vibrio cholerae. J. Biol. Chem. 282: 12860– 12870.
62. Prouty, M. G.,, N. E. Correa, and, K. E. Klose. 2001. The novel sigma54- and sigma28-dependent flagellar gene transcription hierarchy of Vibrio cholerae. Mol. Microbiol. 39: 1595– 1609.
63. Richardson, K. 1991. Roles of motility and flagellar structure in pathogenicity of Vibrio cholerae: analysis of motility mutants in three animal models. Infect. Immun. 59: 1384– 1386.
64. Ryan, R.,, Y. Fouhy,, J. Lucey,, L. Crossman,, S. Spiro,, Y. He,, L. Zhang,, S. Heeb,, M. Camara,, P. Williams, and, J. Dow. 2006. Cell-cell signaling in Xanthomonas campestris involves an HD-GYP domain protein that functions in cyclic di-GMP turnover. Proc. Natl. Acad. Sci. USA 103: 6712– 6717.
65. Ryjenkov, D. A.,, M. Tarutina,, O. V. Moskvin, and M. Go-melsky. 2005. Cyclic diguanylate is a ubiquitous signaling molecule in bacteria: insights into biochemistry of the GGDEF protein domain. J. Bacteriol. 187: 1792– 1793.
66. Schild, S.,, R. Tamayo,, E. J. Nelson,, F. Qadri,, S. B. Calder-wood, and, A. Camilli. 2007. Genes induced late in infection increase fitness of Vibrio cholerae after release into the environment. Cell Host Microbe 2: 264– 277.
67. Schmidt, A. J.,, D. A. Ryjenkov, and, M. Gomelsky. 2005. The ubiquitous protein domain EAL is a cyclic diguanylate-specific phosphodiesterase: enzymatically active and inactive EAL domains. J. Bacteriol. 187: 4774– 4781.
68. Schoolnik, G. K.,, M. I. Voskuil,, D. Schnappinger,, F. H. Yildiz,, K. Meibom,, N. A. Dolganov,, M. A. Wilson, and, K. H. Chong. 2001. Whole genome DNA microarray expression analysis of biofilm development by Vibrio cholerae O1 E1 Tor. Methods Enzymol. 336: 3– 18.
69. Schuhmacher, D. A., and, K. E. Klose. 1999. Environmental signals modulate ToxT-dependent virulence factor expression in Vibrio cholerae. J. Bacteriol. 181: 1508– 1514.
70. Skorupski, K., and, R. K. Taylor. 1999. A new level in the Vibrio cholerae ToxR virulence cascade: AphA is required for transcriptional activation of the tcpPH operon. Mol. Microbiol. 31: 763– 771.
71. Slauch, J. M., and, A. Camilli. 2000. IVET and RIVET: use of gene fusions to identify bacterial virulence factors specifically induced in host tissues. Methods Enzymol. 326: 73– 96.
72. Sudarsan, N.,, E. R. Lee,, Z. Weinberg,, R. H. Moy,, J. N. Kim, K. H. Link, and, R. R. Breaker. 2008. Riboswitches in eubacteria sense the second messenger cyclic di-GMP. Science 321: 411– 413.
73. Tal, R.,, H. C. Wong,, R. Calhoon,, D. Gelfand,, A. L. Fear,, G., Volman,, R. Mayer,, P. Ross,, D. Amikam,, H. Weinhouse,, A. Cohen,, S. Sapir,, P. Ohana, and, M. Benziman. 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.
74. Tamayo, R.,, A. D. Tischler, and, A. Camilli. 2005. The EAL domain protein VieA is a cyclic diguanylate phosphodiesterase. J. Biol. Chem. 280: 33324– 33330.
75. Tamayo, R.,, S. Schild,, J. T. Pratt, and, A. Camilli. 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.
76. Tamplin, M. L.,, A. L. Gauzens,, A. Huq,, D. A. Sack, and, R. R. Colwell. 1990. Attachment of Vibrio cholerae serogroup O1 to zooplankton and phytoplankton of Bangladesh waters. Appl. Environ. Microbiol. 56: 1977– 1980.
77. Taylor, R. K.,, V. L. Miller,, D. B. Furlong, and J. J. Meka-lanos. 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.
78. Tischler, A. D., and, A. Camilli. 2004. Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation. Mol. Microbiol. 53: 857– 869.
79. Tischler, A. D., and, A. Camilli. 2005. Cyclic diguanylate regulates Vibrio cholerae virulence gene expression. Infect. Immun. 73: 5873– 5882.
80. Waldor, M. K., and, J. J. Mekalanos. 1996. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272: 1910– 1914.
81. Watnick, P. I., and, R. Kolter. 1999. Steps in the development of a Vibrio cholerae El Tor biofilm. Mol. Microbiol. 34: 586– 595.
82. Weekly Epidemiological Record. 2007. Cholera, 2006. Wkly. Epidemiol. Rec. 82: 273– 284.
83. Weinberg, Z.,, J. E. Barrick,, Z. Yao,, A. Roth,, J. N. Kim,, J. Gore,, J. X. Wang,, E. R. Lee,, K. F. Block,, N. Sudarsan,, S. Neph,, M. Tompa,, W. L. Ruzzo, and, R. R. Breaker. 2007. Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline. Nucleic Acids Res. 35: 4809– 4819.
84. Yu, R. R., and, V. J. DiRita. 1999. Analysis of an autoregulatory loop controlling ToxT, cholera toxin, and toxin-coregulated pilus production in Vibrio cholerae. J. Bacteriol. 181: 2584– 2592.
85. Zhu, J.,, M. B. Miller,, R. E. Vance,, M. Dziejman,, B. L. Bassler, and, J. J. Mekalanos. 2002. Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. Proc. Natl. Acad.Sci. USA 99: 3129– 3134.

Back to top
This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error