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. 2015 Jan 20;30(1):19–25. doi: 10.1007/s12250-014-3550-7

Survival and proliferation of the lysogenic bacteriophage CTXΦ in Vibrio cholerae

Fenxia Fan 1,✉, Biao Kan 1
PMCID: PMC8200927  PMID: 25613689

Abstract

The lysogenic phage CTXΦ of Vibrio cholerae can transfer the cholera toxin gene both horizontally (inter-strain) and vertically (cell proliferation). Due to its diversity in form and species, the complexity of regulatory mechanisms, and the important role of the infection mechanism in the production of new virulent strains of V. cholerae, the study of the lysogenic phage CTXΦ has attracted much attention. Based on the progress of current research, the genomic features and their arrangement, the host-dependent regulatory mechanisms of CTXΦ phage survival, proliferation and propagation were reviewed to further understand the phage’s role in the evolutionary and epidemiological mechanisms of V. cholerae.

Keywords: Vibrio cholerae, lysogenic bacteriophage, CTXΦ, regulation, evolution

Footnotes

ORCID: 0000-0003-1873-4291

References

  1. Ansaruzzaman M, Bhuiyan N A, Nair B G, Sack D A, Lucas M, Deen J L, Ampuero J, Chaignat C L. Cholera in Mozambique, variant of Vibrio cholerae. Emerg Infect Dis. 2004;10:2057–2059. doi: 10.3201/eid1011.040682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bhattacharya T, Chatterjee S, Maiti D, Bhadra R K, Takeda Y, Nair G B, Nandy R K. Molecular analysis of the rstR and orfU genes of the CTX prophages integrated in the small chromosomes of environmental Vibrio cholerae non-O1, non-O139 strains. Environ Microbiol. 2006;8:52 6–634. doi: 10.1111/j.1462-2920.2005.00932.x. [DOI] [PubMed] [Google Scholar]
  3. Biao K. 1999. Ph.D. thesis. Structure of the Genome of Lysogenic Bacteriophage CTXphi Without Cholera Toxin Gene and Function of its RS Region. Institute of Epidemiology and Microbiology, Chinese Academy of Preventive Medicine, Beijing.
  4. Biao K, Liu Y Q, Qi G M, Zhang L J, Gao S Y. Clone and Analysis of CTXphi Prophage Genome which not Carrying Toxin Gene of Vibrio cholerae. Acta Microbiologica Sinica. 2002;42:573–581. [Google Scholar]
  5. Boyd E F, Waldor M K. Evolutionary and functional analyses of variants of the toxin-coregulated pilus protein TcpA from toxigenic Vibrio cholerae non-O1/non-O139 serogroup isolates. Microbiology. 2002;148:1655–1666. doi: 10.1099/00221287-148-6-1655. [DOI] [PubMed] [Google Scholar]
  6. Boyd E F, Heilpern A J, Waldor M K. Molecular analyses of a putative CTXphi precursor and evidence for independent acquisition of distinct CTX(phi)s by toxigenic Vibrio cholerae. J Bacteriol. 2000;182:5530–5538. doi: 10.1128/JB.182.19.5530-5538.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Click E M, Webster R E. Filamentous phage infection: required interactions with the TolA protein. J Bacteriol. 1997;179:6464–6471. doi: 10.1128/jb.179.20.6464-6471.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Connell T D, Metzger D J, Lynch J, Folster J P. Endochitinase is transported to the extracellular milieu by the eps-encoded general secretory pathway of Vibrio cholerae. J Bacteriol. 1998;180:5591–5600. doi: 10.1128/jb.180.21.5591-5600.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davis B M, Kimsey H H, Chang W, Waldor M K. The Vibrio cholerae O139 Calcutta bacteriophage CTXphi is infectious and encodes a novel repressor. J Bacteriol. 1999;181:6779–6787. doi: 10.1128/jb.181.21.6779-6787.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Davis B M, Kimsey H H, Kane A V, Waldor M K. A satellite phage-encoded antirepressor induces repressor aggregation and cholera toxin gene transfer. EMBO J. 2002;21:4240–4249. doi: 10.1093/emboj/cdf427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Davis B M, Lawson E H, Sandkvist M, Ali A, Sozhamannan S, Waldor M K. Convergence of the secretory pathways for cholera toxin and the filamentous phage, CTXphi. Science. 2000;288:333–335. doi: 10.1126/science.288.5464.333. [DOI] [PubMed] [Google Scholar]
  12. Davis B M, Moyer K E, Boyd E F, Waldor M K. CTX prophages in classical biotype Vibrio cholerae: functional phage genes but dysfunctional phage genomes. J Bacteriol. 2000;182:6992–6998. doi: 10.1128/JB.182.24.6992-6998.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Davis B M, Waldor M K. CTXphi contains a hybrid genome derived from tandemly integrated elements. Proc Natl Acad Sci U S A. 2000;97:8572–8577. doi: 10.1073/pnas.140109997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dziejman M, Balon E, Boyd D, Fraser C M, Heidelberg J F, Mekalanos J J. Comparative genomic analysis of Vibrio cholerae: genes that correlate with cholera endemic and pandemic disease. Proc Natl Acad Sci U S A. 2002;99:1556–1561. doi: 10.1073/pnas.042667999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Faruque S M, Asadulghani, Rahman M M, Waldor M K, Sack D A. Sunlight-induced propagation of the lysogenic phage encoding cholera toxin. Infect Immun. 2000;68:4795–4801. doi: 10.1128/IAI.68.8.4795-4801.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Heidelberg J F, Eisen J A, Nelson W C, Clayton R A, Gwinn M L, Dodson R J, Haft D H, Hickey E K, Peterson J D, Umayam L, Gill S R, Nelson K E, Read T D, Tettelin H, Richardson D, Ermolaeva M D, Vamathevan J, Bass S, Qin H, Dragoi I, Sellers P, McDonald L, Utterback T, Fleishmann R D, Nierman W C, White O, Salzberg S L, Smith H O, Colwell R R, Mekalanos J J, Venter J C, Fraser C M. DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature. 2000;406:477–483. doi: 10.1038/35020000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Heilpern A J, Waldor M K. CTXphi infection of Vibrio cholerae requires the tolQRA gene products. J Bacteriol. 2000;182:1739–1747. doi: 10.1128/JB.182.6.1739-1747.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Heilpern A J, Waldor M K. pIIICTX, a predicted CTXphi minor coat protein, can expand the host range of coliphage fd to include Vibrio cholerae. J Bacteriol. 2003;185:1037–1044. doi: 10.1128/JB.185.3.1037-1044.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Herrington D A, Hall R H, Losonsky G, Mekalanos J J, Taylor R K, Levine M M. Toxin, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans. J Exp Med. 1988;168:1487–1492. doi: 10.1084/jem.168.4.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Huber K E, Waldor M K. Filamentous phage integration requires the host recombinases XerC and XerD. Nature. 2002;417:656–659. doi: 10.1038/nature00782. [DOI] [PubMed] [Google Scholar]
  21. Kamruzzaman M, Robins W P, Bari S M, Nahar S, Mekalanos J J, Faruque S M. RS1 satellite phage promotes diversity of toxigenic Vibrio cholerae by driving CTX prophage loss and elimination of lysogenic immunity. Infect Immun. 2014;82:3636–3643. doi: 10.1128/IAI.01699-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kan B, Qi G M, Liu Y Q, Liu C L, Gao S Y. Genome of bacteriophage CTXφ without the presence of ctxAB exists in ctxAB? strains of Vibrio cholerae. Chin J Microb Immunol. 1999;19:175–179. [Google Scholar]
  23. Kim E J, Lee D, Moon S H, Lee C H, Kim S J, Lee J H, Kim J O, Song M, Das B, Clemens J D, Pape J W, Nair G B, Kim D W. Molecular Insights Into the Evolutionary Pathway of Vibrio cholerae O1 Atypical El Tor Variants. PLoS Pathog. 2014;10:e1004384. doi: 10.1371/journal.ppat.1004384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kimsey H H, Waldor M K. CTXphi immunity: application in the development of cholera vaccines. Proc Natl Acad Sci U S A. 1998;95:7035–7039. doi: 10.1073/pnas.95.12.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kimsey H H, Waldor M K. The CTXphi repressor RstR binds DNA cooperatively to form tetrameric repressor-operator complexes. J Biol Chem. 2004;279:2640–2647. doi: 10.1074/jbc.M311109200. [DOI] [PubMed] [Google Scholar]
  26. Kimsey H H, Waldor M K. Vibrio cholerae LexA coordinates CTX prophage gene expression. J Bacteriol. 2009;191:6788–6795. doi: 10.1128/JB.00682-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kirn T J, Lafferty M J, Sandoe C M, Taylor R K. Delineation of pilin domains required for bacterial association into microcolonies and intestinal colonization by Vibrio cholerae. Mol Microbiol. 2000;35:896–910. doi: 10.1046/j.1365-2958.2000.01764.x. [DOI] [PubMed] [Google Scholar]
  28. Koonin E V. 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. 1992;312:3–6. doi: 10.1016/0014-5793(92)81398-6. [DOI] [PubMed] [Google Scholar]
  29. Krukonis E S, DiRita V J. From motility to virulence: Sensing and responding to environmental signals in Vibrio cholerae. Curr Opin Microbiol. 2003;6:186–190. doi: 10.1016/S1369-5274(03)00032-8. [DOI] [PubMed] [Google Scholar]
  30. Kumar P, Thulaseedharan A, Chowdhury G, Ramamurthy T, Thomas S. Characterization of novel alleles of toxin coregulated pilus A gene (tcpA) from environmental isolates of Vibrio cholerae. Curr Microbiol. 2011;62:758–763. doi: 10.1007/s00284-010-9774-3. [DOI] [PubMed] [Google Scholar]
  31. Li F, Du P, Li B, Ke C, Chen A, Chen J, Zhou H, Li J, Morris J G, Jr., Kan B, Wang D. Distribution of virulence-associated genes and genetic relationships in non-O1/O139 Vibrio cholerae aquatic isolates from China. Appl Environ Microbiol. 2014;80:4987–4992. doi: 10.1128/AEM.01021-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Li M, Kotetishvili M, Chen Y, Sozhamannan S. Comparative genomic analyses of the vibrio pathogenicity island and cholera toxin prophage regions in nonepidemic serogroup strains of Vib rio cholerae. Appl Environ Microbiol. 2003;69:1728–1738. doi: 10.1128/AEM.69.3.1728-1738.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Liu G W, Yan M Y, Qi G M, Gao S Y, Kan B. study on infection of different strains Vibrio cholerae O1 by El tor CTXphi. Acta Microbiologica Sinica. 2005;45:758–762. [PubMed] [Google Scholar]
  34. Maiti D, Das B, Saha A, Nandy R K, Nair G B, Bhadra R K. Genetic organization of pre-CTX and CTX prophages in the genome of an environmental Vibrio cholerae non-O1, non-O139 strain. Microbiology. 2006;152:3633–3641. doi: 10.1099/mic.0.2006/000117-0. [DOI] [PubMed] [Google Scholar]
  35. Meibom K L, Blokesch M, Dolganov N A, Wu C Y, Schoolnik G K. Chitin induces natural competence in Vibrio cholerae. Science. 2005;310:1824–1827. doi: 10.1126/science.1120096. [DOI] [PubMed] [Google Scholar]
  36. Moyer K E, Kimsey H H, Waldor M K. Evidence for a rolling-circle mechanism of phage DNA synthesis from both replicative and integrated forms of CTXphi. Mol Microbiol. 2001;41:311–323. doi: 10.1046/j.1365-2958.2001.02517.x. [DOI] [PubMed] [Google Scholar]
  37. Mukhopadhyay A K, Chakraborty S, Takeda Y, Nair G B, Berg D E. Characterization of VPI pathogenicity island and CTXphi prophage in environmental strains of Vibrio cholerae. J Bacteriol. 2001;183:4737–4746. doi: 10.1128/JB.183.16.4737-4746.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Nair G B, Faruque S M, Bhuiyan N A, Kamruzzaman M, Siddique A K, Sack D A. New variants of Vibrio cholerae O1 biotype El Tor with attributes of the classical biotype from hospitalized patients with acute diarrhea in Bangladesh. J Clin Microbiol. 2002;40:3296–3299. doi: 10.1128/JCM.40.9.3296-3299.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Nandi S, Maiti D, Saha A, Bhadra R K. Genesis of variants of Vibrio cholerae O1 biotype El Tor: role of the CTXphi array and its position in the genome. Microbiology. 2003;149:89–97. doi: 10.1099/mic.0.25599-0. [DOI] [PubMed] [Google Scholar]
  40. Neely M N, Friedman D I. Functional and genetic analysis of regulatory regions of coliphage H-19B: location of shiga-like toxin and lysis genes suggest a role for phage functions in toxin release. Mol Microbiol. 1998;28:1255–1267. doi: 10.1046/j.1365-2958.1998.00890.x. [DOI] [PubMed] [Google Scholar]
  41. Ochman H, Lawrence J G, Groisman E A. Lateral gene transfer and the nature of bacterial innovation. Nature. 2000;405:299–304. doi: 10.1038/35012500. [DOI] [PubMed] [Google Scholar]
  42. Quinones M, Kimsey H H, Waldor M K. LexA cleavage is required for CTX prophage induction. Mol Cell. 2005;17:291–300. doi: 10.1016/j.molcel.2004.11.046. [DOI] [PubMed] [Google Scholar]
  43. Rasched I, Oberer E. Ff coliphages: structural and functional relationships. Microbiol Rev. 1986;50:401–427. doi: 10.1128/mr.50.4.401-427.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Riechmann L, Holliger P. The C-terminal domain of TolA is the coreceptor for filamentous phage infection of E. coli. Cell. 1997;90:351–360. doi: 10.1016/S0092-8674(00)80342-6. [DOI] [PubMed] [Google Scholar]
  45. Russel M. Moving through the membrane with filamentous phages. Trends Microbiol. 1995;3:223–228. doi: 10.1016/S0966-842X(00)88929-5. [DOI] [PubMed] [Google Scholar]
  46. Russel M, Whirlow H, Sun T P, Webster R E. Low-frequency infection of F-bacteria by transducing particles of filamentous bacteriophages. J Bacteriol. 1988;170:5312–5316. doi: 10.1128/jb.170.11.5312-5316.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sandkvist M. Type II secretion and pathogenesis. Infect Immun. 2001;69:3523–3535. doi: 10.1128/IAI.69.6.3523-3535.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Sandkvist M, Michel L O, Hough L P, Morales V M, Bagdasarian M, Koomey M, DiRita V J. General secretion pathway (eps) genes required for toxin secretion and outer membrane biogenesis in Vibrio cholerae. J Bacteriol. 1997;179:6994–7003. doi: 10.1128/jb.179.22.6994-7003.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Sun T P, Webster R E. Nucleotide sequence of a gene cluster involved in entry of E colicins and single-stranded DNA of infecting filamentous bacteriophages into Escherichia coli. J Bacteriol. 1987;169:2667–2674. doi: 10.1128/jb.169.6.2667-2674.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Tacket C O, Taylor R K, Losonsky G, Lim Y, Nataro J P, Kaper J B, Levine M M. Investigation of the roles of toxin-coregulated pili and mannose-sensitive hemagglutinin pili in the pathogenesis of Vibrio cholerae O139 infection. Infect Immun. 1998;66:692–695. doi: 10.1128/iai.66.2.692-695.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Trucksis M, Michalski J, Deng Y K, Kaper J B. The Vibrio cholerae genome contains two unique circular chromosomes. Proc Natl Acad Sci U S A. 1998;95:14464–14469. doi: 10.1073/pnas.95.24.14464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Waldor M K, Mekalanos J J. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science. 1996;272:1910–1914. doi: 10.1126/science.272.5270.1910. [DOI] [PubMed] [Google Scholar]
  53. Waldor M K, Rubin E J, Pearson G D, Kimsey H, Mekalanos J J. Regulation, replication, and integration functions of the Vibrio cholerae CTXphi are encoded by region RS2. Mol Microbiol. 1997;24:917–926. doi: 10.1046/j.1365-2958.1997.3911758.x. [DOI] [PubMed] [Google Scholar]
  54. Wang D, Wang X, Li B, Deng X, Tan H, Diao B, Chen J, Ke B, Zhong H, Zhou H, Ke C, Kan B. High prevalence and diversity of pre-CTXPhi alleles in the environmental Vibrio cholerae O1 and O139 strains in the Zhujiang River estuary. Environ Microbiol Rep. 2014;6:251–258. doi: 10.1111/1758-2229.12121. [DOI] [PubMed] [Google Scholar]
  55. Webster R E. The tol gene products and the import of macromolecules into Escherichia coli. Mol Microbiol. 1991;5:1005–1011. doi: 10.1111/j.1365-2958.1991.tb01873.x. [DOI] [PubMed] [Google Scholar]

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