Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3–5 million reported cases of cholera every year. Historically, there have been seven acknowledged cholera pandemics; recent outbreaks in Zimbabwe and Haiti are included in the seventh and ongoing pandemic1. Only isolates in serogroup O1 (consisting of two biotypes known as ‘classical’ and ‘El Tor’) and the derivative O139 (refs 2, 3) can cause epidemic cholera2. It is believed that the first six cholera pandemics were caused by the classical biotype, but El Tor has subsequently spread globally and replaced the classical biotype in the current pandemic1. Detailed molecular epidemiological mapping of cholera has been compromised by a reliance on sub-genomic regions such as mobile elements to infer relationships, making El Tor isolates associated with the seventh pandemic seem superficially diverse. To understand the underlying phylogeny of the lineage responsible for the current pandemic, we identified high-resolution markers (single nucleotide polymorphisms; SNPs) in 154 whole-genome sequences of globally and temporally representative V. cholerae isolates. Using this phylogeny, we show here that the seventh pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves with a common ancestor in the 1950s, and identify several transcontinental transmission events. Additionally, we show how the acquisition of the SXT family of antibiotic resistance elements has shaped pandemic spread, and show that this family was first acquired at least ten years before its discovery in V. cholerae.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    et al. The origin of the Haitian cholera outbreak strain. N. Engl. J. Med. 364, 33–42 (2011)

  2. 2.

    et al. Comparative genomics reveals mechanism for short-term and long-term clonal transitions in pandemic Vibrio cholerae. Proc. Natl Acad. Sci. USA 106, 15442–15447 (2009)

  3. 3.

    & Site-specific integration of the conjugal Vibrio cholerae SXT element into prfC. Mol. Microbiol. 32, 99–110 (1999)

  4. 4.

    et al. Evolution of MRSA during hospital transmission and intercontinental spread. Science 327, 469–474 (2010)

  5. 5.

    Update:. cholera outbreak—Haiti, 2010. MMWR Morb. Mortal Wkly Rep. 59, 1473–1479 (2010)

  6. 6.

    et al. DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406, 477–483 (2000)

  7. 7.

    et al. Rapid pneumococcal evolution in response to clinical interventions. Science 331, 430–434 (2011)

  8. 8.

    , , & Enhanced Bayesian modelling in BAPS software for learning genetic structures of populations. BMC Bioinformatics 9, 539 (2008)

  9. 9.

    , & Bayesian analysis of genetic differentiation between populations. Genetics 163, 367–374 (2003)

  10. 10.

    , & Evolution of new variants of Vibrio cholerae O1. Trends Microbiol. 18, 46–54 (2010)

  11. 11.

    , & Mobile antibiotic resistance encoding elements promote their own diversity. PLoS Genet. 5, e1000775 (2009)

  12. 12.

    et al. Comparative ICE genomics: insights into the evolution of the SXT/R391 family of ICEs. PLoS Genet. 5, e1000786 (2009)

  13. 13.

    , , , & Evolution of seventh cholera pandemic and origin of 1991 epidemic, Latin America. Emerg. Infect. Dis. 16, 1130–1132 (2010)

  14. 14.

    , , & Relaxed phylogenetics and dating with confidence. PLoS Biol. 4, e88 (2006)

  15. 15.

    et al. The Vibrio seventh pandemic island-II is a 26.9 kb genomic island present in Vibrio cholerae El Tor and O139 serogroup isolates that shows homology to a 43.4 kb genomic island in V. vulnificus. Microbiology 150, 4053–4063 (2004)

  16. 16.

    et al. Molecular characterization of ICEVchVie0 and its disappearance in Vibrio cholerae O1 strains isolated in 2003 in Vietnam. FEMS Microbiol. Lett. 266, 42–48 (2007)

  17. 17.

    et al. Vibrio cholerae O139 in Calcutta, 1992–1998: incidence, antibiograms, and genotypes. Emerg. Infect. Dis. 6, 139–147 (2000)

  18. 18.

    & Pathogenicity islands and phages in Vibrio cholerae evolution. Trends Microbiol. 11, 505–510 (2003)

  19. 19.

    et al. The O139 serogroup of Vibrio cholerae comprises diverse clones of epidemic and nonepidemic strains derived from multiple V. cholerae O1 or non-O1 progenitors. J. Infect. Dis. 182, 1161–1168 (2000)

  20. 20.

    , & Vibrio cholerae O139 Bengal: the eighth pandemic strain of cholera. Indian J. Public Health 38, 33–36 (1994)

  21. 21.

    & The seventh pandemic of cholera. Nature 239, 137–138 (1972)

  22. 22.

    & Velvet: algorithms for de novo short read assembly using de Bruijn graphs. Genome Res. 18, 821–829 (2008)

  23. 23.

    , , , & ABACAS: algorithm-based automatic contiguation of assembled sequences. Bioinformatics 25, 1968–1969 (2009)

  24. 24.

    , , , & Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990)

  25. 25.

    et al. Artemis and ACT: viewing, annotating and comparing sequences stored in a relational database. Bioinformatics 24, 2672–2676 (2008)

  26. 26.

    RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 22, 2688–2690 (2006)

  27. 27.

    et al. Classification of hybrid and altered Vibrio cholerae strains by CTX prophage and RS1 element structure. J. Microbiol. 47, 783–788 (2009)

  28. 28.

    et al. Cholera outbreaks caused by an altered Vibrio cholerae O1 El Tor biotype strain producing classical cholera toxin B in Vietnam in 2007 to 2008. J. Clin. Microbiol. 47, 1568–1571 (2009)

  29. 29.

    & BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol. Biol. 7, 214 (2007)

Download references


This work was supported by The Wellcome Trust grant 076964. The IVI is supported by the Governments of Korea, Sweden and Kuwait. D.W.K. was partially supported by grant RTI05-01-01 from the Ministry of Knowledge and Economy (MKE), Korea and by R01-2006-000-10255-0 from the Korea Science and Engineering Foundation; and J.L.N.W. was supported by the Alborada Trust and the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security. Thanks to A. Camilli at Tufts University Medical School for providing the corrected N16961 sequence, to B.M. Nguyen at NIHE, Vietnam and M. Ansaruzzaman at ICDDR, Bangladesh for providing strains, and to M. Fookes at WTSI for training support.

Author information

Author notes

    • Ankur Mutreja
    • , Dong Wook Kim
    •  & Nicholas R. Thomson

    These authors contributed equally to this work.


  1. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK

    • Ankur Mutreja
    • , Nicholas R. Thomson
    • , Thomas R. Connor
    • , Nicholas J. Croucher
    • , Simon R. Harris
    • , Julian Parkhill
    •  & Gordon Dougan
  2. International Vaccine Institute, SNU Research Park, Bongchun 7 dong, Kwanak, Seoul 151-919, Korea

    • Dong Wook Kim
    • , Je Hee Lee
    • , Seon Young Choi
    • , Eun Jin Kim
    • , John D. Clemens
    •  & Cecil Czerkinsky
  3. Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do 426-791, Korea

    • Dong Wook Kim
  4. Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea

    • Je Hee Lee
    • , Seon Young Choi
    •  & Jongsik Chun
  5. Centre for Microbiology Research, KEMRI at Kenyatta Hosp Compound, Off Ngong RoadPO Box 43640-00100, Kenya

    • Samuel Kariuki
  6. Department of Microbiology and Immunology and University of Gothenburg Vaccine Research Institute, The Sahlgrenska Academy at the University of Gothenburg, Box 435, 40530 Göteborg, Sweden

    • Michael Lebens
    •  & Jan Holmgren
  7. National Institute of Cholera and Enteric Diseases, P-33, CIT Scheme XM, Beliaghata, Kolkata 700 010, India

    • Swapan Kumar Niyogi
    • , T. Ramamurthy
    •  & G. Balakrish Nair
  8. University of Cambridge, Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK

    • James L. N. Wood


  1. Search for Ankur Mutreja in:

  2. Search for Dong Wook Kim in:

  3. Search for Nicholas R. Thomson in:

  4. Search for Thomas R. Connor in:

  5. Search for Je Hee Lee in:

  6. Search for Samuel Kariuki in:

  7. Search for Nicholas J. Croucher in:

  8. Search for Seon Young Choi in:

  9. Search for Simon R. Harris in:

  10. Search for Michael Lebens in:

  11. Search for Swapan Kumar Niyogi in:

  12. Search for Eun Jin Kim in:

  13. Search for T. Ramamurthy in:

  14. Search for Jongsik Chun in:

  15. Search for James L. N. Wood in:

  16. Search for John D. Clemens in:

  17. Search for Cecil Czerkinsky in:

  18. Search for G. Balakrish Nair in:

  19. Search for Jan Holmgren in:

  20. Search for Julian Parkhill in:

  21. Search for Gordon Dougan in:


A.M., D.W.K. and N.R.T. collected the data, analysed it and performed phylogenetic analyses and comparative genomics. J.H.L., S.Y.C., E.J.K. and J.C. analysed the CTX types. S.K., S.K.N. and T.R. were involved in strain collection and serogroup analysis. T.R.C. performed Bayesian analysis; N.J.C. and S.R.H. did the computational coding. J.L.N.W., J.D.C., C.C., G.B.K., J.H., N.R.T., J.P. and G.D. were involved in the study design. A.M., N.R.T., J.P., G.D., J.H., G.B.K., N.J.C., S.R.H., T.R.C., D.W.K. and M.L. contributed to the manuscript writing.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Julian Parkhill.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Figures 1-9 with legends and Supplementary Tables 1-4.

About this article

Publication history






Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.