Chapter 9 : Virulence-Linked Bacteriophages of Pathogenic Vibrios

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

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Virulence-Linked Bacteriophages of Pathogenic Vibrios, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816506/9781555813079_Chap09-1.gif /docserver/preview/fulltext/10.1128/9781555816506/9781555813079_Chap09-2.gif


This chapter focuses on the bacteriophages of pathogenic vibrios, particularly those that have been found to contribute directly to bacterial virulence. These phages primarily target ; however, a virulence-associated phage found in is also discussed briefly. O139 appears to have evolved from an O1 El Tor strain that acquired a new cassette of genes for O antigen production. Whether the emergence of O139 as a widespread etiologic agent of cholera marks the beginning of a new, eighth cholera pandemic is being debated. The 5’ end of the prophage (-2.4 kb) is known as the RS region. It encodes proteins needed for phage gene regulation (RstR), phage replication (RstA), and phage DNA integration (RstB). Genetic studies indicate that at least two protein complexes are used by CTXφ to infect . Toxin-coregulated pilus (TCP), a homopolymer of TcpA, is thought to be CTXφ’s primary receptor. A hybrid Fd phage that displays the N-terminal and central domains of pIII on its surface was able to infect , suggesting that pIII is the only CTXφ protein that is needed for normal recognition and infection of its host. Studies of the lysogenic filamentous phage have yielded knowledge of new types of virus-host interactions. The authors anticipate that future studies of CTXφ will provide additional examples of how a virus and its host can coevolve in a symbiotic fashion. Furthermore, it seems likely that future studies of other pathogenic vibrios will uncover new bacteriophages that influence pathogenicity.

Citation: Davis B, Waldor M. 2005. Virulence-Linked Bacteriophages of Pathogenic Vibrios, p 187-205. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch9

Key Concept Ranking

Type II Secretion System
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

(Top) Schematic diagram of the CTXϕ genome, drawn roughly to scale.Arrows show genes and the direction of transcription. Bent arrows represent the , , and promoters. Solid triangles represent the 15-bp repeats found at each end of the prophage. Protein functions are indicated underneath the genes.The overall organization of the CTXϕ genome is similar to those of other filamentous phages from species and of filamentous phages from . (Middle) Graph of the G+C content of the CTXϕ genome, calculated by use of a 100-bp sliding window.The G+C contents of and differ the most dramatically from the average %G+C.The G+C contents of and the promoter were calculated for . (Bottom) Schematic diagram of RS1, a satellite phage related to CTXϕ.

Citation: Davis B, Waldor M. 2005. Virulence-Linked Bacteriophages of Pathogenic Vibrios, p 187-205. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Schematic representation of CTXϕ integration.The chromosomal integration site () recombines with the integration site in pCTX () through short regions of homology (white rectangles; equivalent to the solid triangles seen in Fig. 1 ).This process yields a single integrated prophage.

Citation: Davis B, Waldor M. 2005. Virulence-Linked Bacteriophages of Pathogenic Vibrios, p 187-205. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Arrangement of CTX prophage and RS1 DNA integrated in a variety of clinical isolates of . Most O1 El Tor biotype strains and O139 strains (all of those shown here) have CTXϕ DNA integrated into the large chromosome (chrI). Phage DNA is typically part of an array of tandemly integrated elements.We have found that strain N16961 has two copies of RS1 that flank a prophage rather than a single RS1 element downstream of the prophage, as was reported previously ( ). O1 classical biotype strains have CTXϕ DNA integrated into both chromosomes. Each chromosome has either a single prophage or an array of two truncated, fused prophages.

Citation: Davis B, Waldor M. 2005. Virulence-Linked Bacteriophages of Pathogenic Vibrios, p 187-205. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

Production of extrachromosomal CTXϕ DNA from a prophage array relies on a replicative process mediated by RstA. Phage DNA excision does not occur. Replication initiates at the origin of replication, which lies near the 3′ end of . As the replication complex moves along the phage DNA template, it displaces a single strand of the phage genome and replaces it with a newly synthesized strand. Replication continues past the end of the prophage, into the adjacent element downstream (in this case, RS1). Replication terminates at the origin of replication of the downstream element. A single-stranded hybrid phage genome, containing DNA from both the upstream and downstream elements in the array, is then released.

Citation: Davis B, Waldor M. 2005. Virulence-Linked Bacteriophages of Pathogenic Vibrios, p 187-205. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch9
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Albert, M. J.,, N. A. Bhuiyan,, A. Rahman,, A. N. Ghosh,, K. Hultenby,, A. Weintraub,, S. Nahar,, A. K. Kibriya,, M. Ansaruzzaman,, and T. Shimada. 1996. Phage specific for Vibrio cholerae O139 Bengal. J. Clin. Microbiol. 34:18431845.
2. Attridge, S. R.,, A. Fazeli,, P. A. Manning,, and U. H. Stroeher. 2001. Isolation and characterization of bacteriophage-resistant mutants of Vibrio cholerae O139. Microb. Pathog. 30:237246.
3. Barua, D., 1992. History of cholera, p. 136. In D. Barua, and I. W. B. Greenough (ed.), Cholera. Plenum Press, New York, N.Y.
4. Basu, A.,, A. K. Mukhopadhyay,, C. Sharma,, J. Jyot,, A. Gupta,, A. Ghosh,, S. K. Bhattacharya,, Y. Takeda,, A. S. Faruque,, M. J. Albert,, and G. B. Nair. 1998. Heterogeneity in the organization of the CTX genetic element in strains of Vibrio cholerae O139 isolated from Calcutta, India and Dhaka, Bangladesh and its possible link to the dissimilar incidence of O139 cholera in the two locales. Microb. Pathog. 24:175183.
5. Baudry, B.,, A. Fasano,, J. Ketley,, and J. B. Kaper. 1992. Cloning of a gene (zot) encoding a new toxin produced by Vibrio cholerae. Infect.Immun. 60:428434.
6. Bhuiyan, N. A.,, M. Ansaruzzaman,, M. Kamruzzaman,, K. Alam,, N. R. Chowdhury,, M. Nishibuchi,, S. M. Faruque,, D. A. Sack,, Y. Takeda,, and G. B. Nair. 2002. Prevalence of the pandemic genotype of Vibrio parahaemolyticus in Dhaka, Bangladesh, and significance of its distribution across different serotypes. J. Clin. Microbiol. 40:284286.
7. Bik, E. M.,, A. E. Bunschoten,, R.D. Gouw,, and F. R. Mooi. 1995. Genesis of the novel epidemic Vibrio cholerae O139 strain: evidence for horizontal transfer of genes involved in polysaccharide synthesis. EMBO J. 14:209216.
8. Boyd, E. F.,, A. J. Heilpern,, and M. K. Waldor. 2000. Molecular analyses of a putative CTXφ precursor and evidence for independent acquisition of distinct CTXφs by toxigenic Vibrio cholerae. J. Bacteriol. 182:55305538.
9. Boyd, E. F.,, K. E. Moyer,, L. Shi,, and M. K. Waldor. 2000. Infectious CTXφ and the vibrio pathogenicity island prophage in Vibrio mimicus: evidence for recent horizontal transfer between V. mimicus and V. cholerae. Infect.Immun. 68:15071513.
10. Boyd, E. F.,, and M. K. Waldor. 1999. Alternative mechanism of cholera toxin acquisition by Vibrio cholerae: generalized transduction of CTXφ by bacteriophage CP-T1. Infect.Immun. 67:58985905.
11. Boyd, E. F.,, and M. K. Waldor. 2002. Evolutionary and functional analyses of variants of the toxin-coregulated pilus protein TcpA from toxigenic Vibrio cholerae non-O1/non-O139 serogroup isolates. Microbiology 148:16551666.
12. Campbell, A. P.,, and D. Botstein,. 1983. Evolution of the lambdoid phages, p. 365380. In R. Hendrix,, J. Roberts,, F. Stahl,, and R. Weisberg (ed.), Lambda II. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.
13. Campos, J.,, E. Martinez,, K. Marrero,, Y. Silva,, B. L. Rodriguez,, E. Suzarte,, T. Ledon,, and R. Fando. 2003. Novel type of specialized transduction for CTXφ or its satellite phage RS1 mediated by filamentous phage VGJφ in Vibrio cholerae. J. Bacteriol. 185:72317240.
14. Campos, J.,, E. Martinez,, E. Suzarte,, B. L. Rodriguez,, K. Marrero,, Y. Silva,, T. Ledon,, R. del Sol,, and R. Fando. 2003.VGJφ, a novel filamentous phage of Vibrio cholerae, integrates into the same chromosomal site as CTXφ. J. Bacteriol. 185:56855696.
15. Chang, B.,, H. Taniguchi,, H. Miyamoto,, and S. Yoshida. 1998. Filamentous bacteriophages of Vibrio parahaemolyticus as a possible clue to genetic transmission. J. Bacteriol. 180:50945101.
16.Cholera Working Group. 1993. Large epidemic of cholera-like disease in Bangladesh caused by Vibrio cholerae O139 synonym Bengal. Lancet 342:387390.
17. Click, E. M.,, and R. E. Webster. 1998. The TolQRA proteins are required for membrane insertion of the major capsid protein of the filamentous phage f1 during infection. J. Bacteriol. 180: 17231728.
18. Dalsgaard, A.,, O. Serichantalergs,, A. Forslund,, W. Lin,, J. Mekalanos,, E. Mintz,, T. Shimada,, and J. G. Wells. 2001. Clinical and environmental isolates of Vibrio cholerae serogroup O141 carry the CTX phage and the genes encoding the toxincoregulated pili. J. Clin. Microbiol. 39:40864092.
19. Davis, B. M.,, H. H. Kimsey,, W. Chang,, and M. K. Waldor. 1999.The Vibrio cholerae O139 Calcutta bacteriophage CTXφ is infectious and encodes a novel repressor. J. Bacteriol. 181:67796787.
20. Davis, B. M.,, H. H. Kimsey,, A.V. Kane,, and M. K. Waldor. 2002. A satellite phage-encoded antirepressor induces repressor aggregation and cholera toxin gene transfer. EMBO J. 21:42404249.
21. Davis, B. M.,, E. H. Lawson,, M. Sandkvist,, A. Ali,, S. Sozhamannan,, and M. K. Waldor. 2000. Convergence of the secretory pathways for cholera toxin and the filamentous phage, CTXφ. Science 288:333335.
22. Davis, B. M.,, K. E. Moyer,, E. F. Boyd,, and M. K. Waldor. 2000. CTX prophages in classical biotype Vibrio cholerae: functional phage genes but dysfunctional phage genomes. J. Bacteriol. 182:69926998.
23. Davis, B. M.,, and M. K. Waldor. 2000. CTXφ contains a hybrid genome derived from tandemly integrated elements. Proc. Natl. Acad. Sci. USA 97:85728577.
24. Davis, B. M.,, and M. K. Waldor. 2003. Filamentous phages linked to virulence of Vibrio cholerae. Curr. Opin. Microbiol. 6:3542.
25. Deng, L. W.,, P. Malik,, and R. N. Perham. 1999. Interaction of the globular domains of pIII protein of filamentous bacteriophage fd with the Fpilus of Escherichia coli. Virology 253:271277.
26. Di Pierro, M.,, R. Lu,, S. Uzzau,, W. Wang,, K. Margaretten,, C. Pazzani,, F. Maimone,, and A. Fasano. 2001. Zonula occludens toxin structurefunction analysis. Identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain. J. Biol. Chem. 276:1916019165.
27. DiRita, V. J.,, C. Parsot,, G. Jander,, and J. J. Mekalanos. 1991. Regulatory cascade controls virulence in Vibrio cholerae. Proc. Natl.Acad. Sci.USA 88:54035407.
28. Ehara, M.,, S. Shimodori,, F. Kojima,, Y. Ichinose,, T. Hirayama,, M. J. Albert,, K. Supawat,, Y. Honma,, M. Iwanaga,, and K. Amako. 1997. Characterization of filamentous phages of Vibrio cholerae O139 and O1. FEMS Microbiol. Lett. 154:293301.
29. Eroshenko, G.A.,, and N. I. Smirnova. 2002. Alteration of cholera toxin biosynthesis in Vibrio cholerae 01 as a result of temperate phage 139 integration into bacterial chromosome. Mol. Gen. Mikrobiol. Virusol. 2002:914.
30. Estrem, S. T.,, T. Gaal,, W. Ross,, and R. L. Gourse. 1998. Identification of an UP element consensus sequence for bacterial promoters. Proc. Natl.Acad. Sci. USA 95:97619766.
31. Faruque, S. M., Asadulghani, M. Kamruzzaman, R. K. Nandi, A. N. Ghosh, G. B. Nair, J. J. Mekalanos, and D. A. Sack. 2002. RS1 element of Vibrio cholerae can propagate horizontally as a filamentous phage exploiting the morphogenesis genes of CTXφ. Infect. Immun. 70:163170.
32. Faruque, S. M.,Asadulghani, M. M. Rahman, M. K.Waldor, and D. A. Sack. 2000. Sunlightinduced propagation of the lysogenic phage encoding cholera toxin. Infect.Immun. 68:47954801.
33. Faruque, S. M.,, N. Chowdhury,, M. Kamruzzaman,, Q. S. Ahmad,, A. S. Faruque,, M. A. Salam,, T. Ramamurthy,, G. B. Nair,, A. Weintraub,, and D. A. Sack. 2003. Reemergence of epidemic Vibrio cholerae O139, Bangladesh. Emerg. Infect. Dis. 9:11161122.
34. Faruque, S. M.,, M. Kamruzzaman, Asadulghani, D. A. Sack, J. J. Mekalanos, and G. B. Nair. 2003. CTXφ-independent production of the RS1 satellite phage by Vibrio cholerae. Proc. Natl. Acad. Sci. USA 100:12801285.
35. Faruque, S. M.,, M. M. Rahman,Asadulghani, K. M. Nasirul Islam, and J. J. Mekalanos. 1999. Lysogenic conversion of environmental Vibrio mimicus strains by CTXφ. Infect.Immun. 67:57235729.
36. Faruque, S. M.,, J. Zhu,Asadulghani, M. Kamruzzaman, and J. J. Mekalanos. 2003. Examination of diverse toxin-coregulated pilus-positive Vibrio cholerae strains fails to demonstrate evidence for vibrio pathogenicity island phage. Infect.Immun. 71:29932999.
37. Fasano, A.,, B. Baudry,, D.W. Pumplin,, S. S. Wasserman,, B. D. Tall,, J. M. Ketley,, and J. B. Kaper. 1991. Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions. Proc. Natl.Acad. Sci. USA 88:52425246.
38. Gonzalez, M. D.,, C. A. Lichtensteiger,, R. Caughlan,, and E. R. Vimr. 2002. Conserved filamentous prophage in Escherichia coli O18:K1:H7 and Yersinia pestis biovar orientalis. J. Bacteriol. 184:60506055.
39. Hase, C. C.,, and J. J. Mekalanos. 1998.TcpP protein is a positive regulator of virulence gene expression in Vibrio cholerae. Proc. Natl.Acad. Sci.USA 95:730734.
40. Heidelberg, J. F.,, J. A. Eisen,, W. C. Nelson,, R. A. Clayton,, M. L. Gwinn,, R. J. Dodson,, D. H. Haft,, E. K. Hickey,, J. D. Peterson,, L. Umayam,, S. R. Gill,, K. E. Nelson,, T.D. Read,, H. Tettelin,, D. Richardson,, M.D. Ermolaeva,, J. Vamathevan,, S. Bass,, H. Qin,, I. Dragoi,, P. Sellers,, L. McDonald,, T. Utterback,, R. D. Fleishmann,, W. C. Nierman,, O. White,, S. L. Salzberg,, H. O. Smith,, R. R. Colwell,, J. J. Mekalanos,, J. C. Venter,, and C. M. Fraser. 2000. DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406:477483.
41. Heilpern, A. J.,, and M. K. Waldor. 2000.CTXφ infection of Vibrio cholerae requires the tolQRA gene products. J. Bacteriol. 182:17391747.
42. Heilpern, A. J.,, and M. K. Waldor. 2003. pIIICTX, a predicted CTXφ minor coat protein, can expand the host range of coliphage fd to include Vibrio cholerae. J. Bacteriol. 185:10371044.
43. 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. 168:14871492.
44. Holliger, P.,, and L. Riechmann. 1997.A conserved infection pathway for filamentous bacteriophages is suggested by the structure of the membrane penetration domain of the minor coat protein g3p from phage fd. Structure 5:265275.
45. Huber, K. E. 2002. Replication and integration of the Vibrio cholerae filamentous bacteriophage CTXφ. Ph.D. thesis. Tufts University, Boston, Mass.
46. Huber, K. E.,, and M. K. Waldor. 2002. Filamentous phage integration requires the host recombinases XerC and XerD. Nature 417:656659.
47. Iida, T.,, K. Makino,, H. Nasu,, K. Yokoyama,, K. Tagomori,, A. Hattori,, T. Okuno,, H. Shinagawa,, and T. Honda. 2002. Filamentous bacteriophages of vibrios are integrated into the dif-like site of the host chromosome. J. Bacteriol. 184:49334935.
48. Ikema, M.,, and Y. Honma. 1998. A novel filamentous phage, fs-2, of Vibrio cholerae O139. Microbiology 144:19011906.
49. Iwanaga, M.,, K. Yamamoto,, N. Higa,, Y. Ichinose,, N. Nakasone,, and M. Tanabe. 1986. Culture conditions for stimulating cholera toxin production by Vibrio cholerae O1 El Tor. Microbiol. Immunol. 30:10751083.
50. Jacobson, A. 1972. Role of F pili in the penetration of bacteriophage fl. J.Virol. 10:835843.
51. Jouravleva, E. A.,, G. A. McDonald,, C. F. Garon,, M. Boesman-Finkelstein,, and R. A. Finkelstein. 1998. Characterization and possible functions of a new filamentous bacteriophage from Vibrio cholerae O139. Microbiology 144:315324.
52. Jouravleva, E.A.,, G.A. McDonald,, J.W. Marsh,, R. K. Taylor,, M. Boesman-Finkelstein,, and R.A. Finkelstein. 1998.The Vibrio cholerae mannose-sensitive hemagglutinin is the receptor for a filamentous bacteriophage from V. cholerae O139.Infect. Immun. 66:25352539.
53. Kaper, J. B.,, J. G. Morris, Jr.,, and M. M. Levine. 1995. Cholera. Clin. Microbiol. Rev. 8:4886.
54. Karaolis, D. K.,, S. Somara,, D. R. Maneval, Jr.,, J. A. Johnson,, and J. B. Kaper. 1999.A bacteriophage encoding a pathogenicity island, a type- IV pilus and a phage receptor in cholera bacteria. Nature 399:375379.
55. Kimsey, H.,, and M. K. Waldor. 2003. The CTXφ repressor RstR binds DNA cooperatively to form tetrameric repressor:operator complexes. J. Biol. Chem. 279:26402647.
56. Kimsey, H. H.,, G. B. Nair,, A. Ghosh,, and M. K. Waldor. 1998. Diverse CTXφs and evolution of new pathogenic Vibrio cholerae. Lancet 352:457458.
57. Kimsey, H. H.,, and M. K. Waldor. 1998.CTXφ immunity: application in the development of cholera vaccines. Proc. Natl.Acad. Sci.USA 95:70357039.
58. 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. 35:896910.
59. Koonin, E. V. 1992. The second cholera toxin, Zot, and its plasmid-encoded and phage-encoded homologues constitute a group of putative ATPases with an altered purine NTP-binding motif. FEBS Lett. 312:36.
60. Lazar, S.,, and M. K. Waldor. 1998. ToxR-independent expression of cholera toxin from the replicative form of CTXφ. Infect. Immun. 66:394397.
61. 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 99:625634.
62. Li, M.,, M. Kotetishvili,, Y. Chen,, and S. Sozhamannan. 2003. Comparative genomic analyses of the vibrio pathogenicity island and cholera toxin prophage regions in non-epidemic serogroup strains of Vibrio cholerae. Appl. Environ. Microbiol. 69:17281738.
63. Linnerborg, M.,, A. Weintraub,, M. J. Albert,, and G. Widmalm. 2001. Depolymerization of the capsular polysaccharide from Vibrio cholerae O139 by a lyase associated with the bacteriophage JA1. Carbohydr. Res. 333:263269.
64. Longini, I. M., Jr.,, M. Yunus,, K. Zaman,, A. K. Siddique,, R. B. Sack,, and A. Nizam. 2002. Epidemic and endemic cholera trends over a 33-year period in Bangladesh. J. Infect. Dis. 186:246251.
65. Lubkowski, J.,, F. Hennecke,, A. Pluckthun,, and A. Wlodawer. 1999. Filamentous phage infection: crystal structure of g3p in complex with its coreceptor, the C-terminal domain of TolA. Struct. Fold Des. 7:711722.
66. Makino, K.,, K. Oshima,, K. Kurokawa,, K. Yokoyama,, T. Uda,, K. Tagomori,, Y. Iijima,, M. Najima,, M. Nakano,, A. Yamashita,, Y. Kubota,, S. Kimura,, T. Yasunaga,, T. Honda,, H. Shinagawa,, M. Hattori,, and T. Iida. 2003. Genome sequence of Vibrio parahaemolyticus: a pathogenic mechanism distinct from that of V. cholerae. Lancet 361:743749.
67. Matsumoto, C.,, J. Okuda,, M. Ishibashi,, M. Iwanaga,, P. Garg,, T. Rammamurthy,, H. C. Wong,, A. Depaola,, Y.B. Kim,, M. J. Albert,, and M. Nishibuchi. 2000. Pandemic spread of an O3:K6 clone of Vibrio parahaemolyticus and emergence of related strains evidenced by arbitrarily primed PCR and toxRS sequence analyses. J. Clin. Microbiol. 38:578585.
68. McCleod, S. M.,, and M. K. Waldor. 2004. Characterization of XerC and XerD-dependent CTX phage integration in Vibrio cholerae. Mol. Microbiol. 54:935947.
69. Mekalanos, J. J. 1983. Duplication and amplification of toxin genes in Vibrio cholerae. Cell 35:253263.
70. Mitra, S.N.,, R. Mukhopadhyay,, A.N. Ghosh,, and R. K. Ghosh. 2000. Conversion of Vibrio El Tor MAK757 to classical biotype: role of phage PS166. Virology 273:3643.
71. Morris, J. G., Jr. 2003. Cholera and other types of vibriosis: a story of human pandemics and oysters on the half shell. Clin. Infect. Dis. 37:272280.
72. Moyer, K. E.,, H. H. Kimsey,, and M. K. Waldor. 2001. Evidence for a rolling-circle mechanism of phage DNA synthesis from both replicative and integrated forms of CTXφ. Mol. Microbiol. 41:311323.
73. Mukhopadhyay, A. K.,, S. Chakraborty,, Y. Takeda,, G.B. Nair,, and D. E. Berg. 2001. Characterization of VPI pathogenicity island and CTXφ prophage in environmental strains of Vibrio cholerae. J. Bacteriol. 183:47374746.
74. Nandi, S.,, D. Maiti,, A. Saha,, and R. K. Bhadra. 2003. Genesis of variants of Vibrio cholerae O1 biotype El Tor: role of the CTXφ array and its position in the genome. Microbiology 149:8997.
75. Nasu, H.,, T. Iida,, T. Sugahara,, Y. Yamaichi,, K. S. Park,, K. Yokoyama,, K. Makino,, H. Shinagawa,, and T. Honda. 2000.A filamentous phage associated with recent pandemic Vibrio parahaemolyticus O3:K6 strains. J. Clin. Microbiol. 38: 21562161.
76. Nesper, J.,, J. Blass,, M. Fountoulakis,, and J. Reidl. 1999. Characterization of the major control region of Vibrio cholerae bacteriophage K139: immunity, exclusion, and integration. J. Bacteriol. 181:29022913.
77. Nesper, J.,, D. Kapfhammer,, K. E. Klose,, H. Merkert,, and J. Reidl. 2000. Characterization of Vibrio cholerae O1 antigen as the bacteriophage K139 receptor and identification of IS1004 insertions aborting O1 antigen biosynthesis. J. Bacteriol. 182:50975104.
78. Ogg, J. E.,, M. B. Shrestha,, and L. Poudayl. 1978. Phage-induced changes in Vibrio cholerae: serotype and biotype conversions. Infect. Immun. 19:231238.
79. Pearson, G. D.,, A. Woods,, S. L. Chiang,, and J. J. Mekalanos. 1993. CTX genetic element encodes a site-specific recombination system and an intestinal colonization factor. Proc. Natl. Acad. Sci. USA 90:37503754.
80. Pearson, G.D.N. 1989. The cholera toxin genetic element: a site specific transposon. Ph.D. thesis. Harvard University Medical School, Boston, Mass.
80a. Quinones, M.,, H. H. Kimsey,, and M. K. Waldor. 2005. LexA cleavage is required for CTX prophage induction. Mol. Cell 17:291300.
81. Reidl, J.,, and J. J. Mekalanos. 1995. Characterization of Vibrio cholerae bacteriophage K139 and use of a novel mini-transposon to identify a phageencoded virulence factor.Mol.Microbiol.18:685701.
82. Riechmann, L.,, and P. Holliger. 1997. The C-terminal domain ofTolA is the coreceptor for filamentous phage infection of E.coli.Cell 90:351360.
83. Russel, M. 1995.Moving through the membrane with filamentous phages.Trends Microbiol.3:223228.
84. Sandkvist, M.,, L.O. Michel,, L. P. Hough,, V. M. Morales,, M. Bagdasarian,, M. Koomey,, and V. J. DiRita. 1997. General secretion pathway (eps) genes required for toxin secretion and outer membrane biogenesis in Vibrio cholerae. J. Bacteriol. 179:69947003.
85. Scott, M. E.,, Z.Y. Dossani,, and M. Sandkvist. 2001. Directed polar secretion of protease from single cells of Vibrio cholerae via the type II secretion pathway. Proc. Natl.Acad. Sci.USA 98:1397813983.
86. Skorupski, K.,, and R. K. Taylor. 1997. Control of the ToxR virulence regulon in Vibrio cholerae by environmental stimuli. Mol. Microbiol. 25:10031009.
87. Trucksis, M.,, T. L. Conn,, S. S. Wasserman,, and C. L. Sears. 2000. Vibrio cholerae ACE stimulates Ca(2+)-dependent Cl()/HCO3(-) secretion in T84 cells in vitro. Am. J. Physiol. Cell Physiol. 279:C567C577.
88. Trucksis, M.,, J. E. Galen,, J. Michalski,, A. Fasano,, and J. B. Kaper. 1993.Accessory cholera enterotoxin (Ace), the third toxin of a Vibrio cholerae virulence cassette. Proc. Natl. Acad. Sci. USA 90: 52675271.
89. Uzzau, S.,, P. Cappuccinelli,, and A. Fasano. 1999. Expression of Vibrio cholerae zonula occludens toxin and analysis of its subcellular localization. Microb. Pathog. 27:377385.
90. Wachsmuth, K.,, O. Olsvik,, M. M. Evins,, and T. Popovic,. 1994. Molecular epidemiology of cholera, p. 357370. In K. Wachsmuth,, P. A. Blake,, and O. Olsvik (ed.),Vibrio cholerae and Cholera: Molecular to Global Perspectives. American Society for Microbiology, Washington, D.C.
91. Wagner, P. L.,, J. Livny,, M. N. Neely,, D.W. Acheson,, D. I. Friedman,, and M. K. Waldor. 2002. Bacteriophage control of Shiga toxin 1 production and release by Escherichia coli. Mol. Microbiol. 44:957970.
92. Wagner, P. L.,, M. N. Neely,, X. Zhang,, D.W. Acheson,, M. K. Waldor,, and D. I. Friedman. 2001. Role for a phage promoter in Shiga toxin 2 expression from a pathogenic Escherichia coli strain. J. Bacteriol. 183:20812085.
93. Waldor, M. K.,, and J. J. Mekalanos. 1996. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272:19101914.
94. Waldor, M. K.,, E. J. Rubin,, G. D. Pearson,, H. Kimsey,, and J. J. Mekalanos. 1997. Regulation, replication, and integration functions of the Vibrio cholerae CTXφ are encoded by region RS2. Mol. Microbiol. 24:917926.
95. Xu, Q.,, M. Dziejman,, and J. J. Mekalanos. 2003. Determination of the transcriptome of Vibrio cholerae during intraintestinal growth and midexponential phase in vitro. Proc. Natl.Acad. Sci.USA 100:12861291.

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