Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe


Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery1,2, spreading efficiently via low-dose fecal-oral transmission3,4. Historically, S. sonnei has been predominantly responsible for dysentery in developed countries but is now emerging as a problem in the developing world, seeming to replace the more diverse Shigella flexneri in areas undergoing economic development and improvements in water quality4,5,6. Classical approaches have shown that S. sonnei is genetically conserved and clonal7. We report here whole-genome sequencing of 132 globally distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and that diversified into several distinct lineages with unique characteristics. Our analysis suggests that the majority of this diversification occurred in Europe and was followed by more recent establishment of local pathogen populations on other continents, predominantly due to the pandemic spread of a single, rapidly evolving, multidrug-resistant lineage.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Figure 1: Bayesian maximum clade credibility phylogeny for S. sonnei.

Accession codes

Primary accessions

European Nucleotide Archive

Referenced accessions

European Nucleotide Archive

NCBI Reference Sequence


  1. Pupo, G.M., Lan, R. & Reeves, P.R. Multiple independent origins of Shigella clones of Escherichia coli and convergent evolution of many of their characteristics. Proc. Natl. Acad. Sci. USA 97, 10567–10572 (2000).

    Article  CAS  Google Scholar 

  2. Yang, F. et al. Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery. Nucleic Acids Res. 33, 6445–6458 (2005).

    Article  Google Scholar 

  3. DuPont, H.L., Levine, M.M., Hornick, R.B. & Formal, S.B. Inoculum size in shigellosis and implications for expected mode of transmission. J. Infect. Dis. 159, 1126–1128 (1989).

    Article  CAS  Google Scholar 

  4. Kotloff, K.L. et al. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull. World Health Organ. 77, 651–666 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Sack, D.A., Hoque, A.T., Huq, A. & Etheridge, M. Is protection against shigellosis induced by natural infection with Plesiomonas shigelloides? Lancet 343, 1413–1415 (1994).

    Article  CAS  Google Scholar 

  6. Vinh, H. et al. A changing picture of shigellosis in southern Vietnam: shifting species dominance, antimicrobial susceptibility and clinical presentation. BMC Infect. Dis. 9, 204 (2009).

    Article  Google Scholar 

  7. Karaolis, D.K., Lan, R. & Reeves, P.R. Sequence variation in Shigella sonnei (Sonnei), a pathogenic clone of Escherichia coli, over four continents and 41 years. J. Clin. Microbiol. 32, 796–802 (1994).

    Article  CAS  Google Scholar 

  8. Drummond, A.J. & Rambaut, A. BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol. Biol. 7, 214 (2007).

    Article  Google Scholar 

  9. Nastasi, A., Pignato, S., Mammina, C. & Giammanco, G. rRNA gene restriction patterns and biotypes of Shigella sonnei. Epidemiol. Infect. 110, 23–30 (1993).

    Article  CAS  Google Scholar 

  10. Touchon, M. et al. CRISPR distribution within the Escherichia coli species is not suggestive of immunity-associated diversifying selection. J. Bacteriol. 193, 2460–2467 (2011).

    Article  CAS  Google Scholar 

  11. Mutreja, A. et al. Evidence for several waves of global transmission in the seventh cholera pandemic. Nature 477, 462–465 (2011).

    Article  CAS  Google Scholar 

  12. Morelli, G. et al. Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity. Nat. Genet. 42, 1140–1143 (2010).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Parker, J., Rambaut, A. & Pybus, O.G. Correlating viral phenotypes with phylogeny: accounting for phylogenetic uncertainty. Infect. Genet. Evol. 8, 239–246 (2008).

    Article  CAS  Google Scholar 

  15. Ranjbar, R. et al. Genetic relatedness among isolates of Shigella sonnei carrying class 2 integrons in Tehran, Iran, 2002–2003. BMC Infect. Dis. 7, 62 (2007).

    Article  Google Scholar 

  16. Holt, K.E. et al. High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi. Nat. Genet. 40, 987–993 (2008).

    Article  CAS  Google Scholar 

  17. World Health Organization. Guidelines for the Control of Shigellosis, Including Epidemics Due to Shigella dysenteriae Type 1 (WHO Document Production Services, Geneva, 2005).

  18. Christopher, P.R., David, K.V., John, S.M. & Sankarapandian, V. Antibiotic therapy for Shigella dysentery. Cochrane Database Syst. Rev. CD006784 (2010).

  19. Vinh, H. et al. A multi-center randomized trial to assess the efficacy of gatifloxacin versus ciprofloxacin for the treatment of shigellosis in Vietnamese children. PLoS Negl. Trop. Dis. 5, e1264 (2011).

    Article  CAS  Google Scholar 

  20. Vinh, H. et al. Treatment of bacillary dysentery in Vietnamese children: two doses of ofloxacin versus 5-days nalidixic acid. Trans. R. Soc. Trop. Med. Hyg. 94, 323–326 (2000).

    Article  CAS  Google Scholar 

  21. Jeong, H.J. et al. Acanthamoeba: could it be an environmental host of Shigella? Exp. Parasitol. 115, 181–186 (2007).

    Article  CAS  Google Scholar 

  22. Saeed, A., Abd, H., Edvinsson, B. & Sandstrom, G. Acanthamoeba castellanii an environmental host for Shigella dysenteriae and Shigella sonnei. Arch. Microbiol. 191, 83–88 (2009).

    Article  CAS  Google Scholar 

  23. Winiecka-Krusnell, J. & Linder, E. Free-living amoebae protecting Legionella in water: the tip of an iceberg? Scand. J. Infect. Dis. 31, 383–385 (1999).

    Article  CAS  Google Scholar 

  24. Greub, G. & Raoult, D. Microorganisms resistant to free-living amoebae. Clin. Microbiol. Rev. 17, 413–433 (2004).

    Article  Google Scholar 

  25. Shepherd, J.G., Wang, L. & Reeves, P.R. Comparison of O-antigen gene clusters of Escherichia coli (Shigella) sonnei and Plesiomonas shigelloides O17: sonnei gained its current plasmid-borne O-antigen genes from P. shigelloides in a recent event. Infect. Immun. 68, 6056–6061 (2000).

    Article  CAS  Google Scholar 

  26. Sansonetti, P.J., Kopecko, D.J. & Formal, S.B. Shigella sonnei plasmids: evidence that a large plasmid is necessary for virulence. Infect. Immun. 34, 75–83 (1981).

    Article  CAS  Google Scholar 

  27. Van de Verg, L.L., Herrington, D.A., Boslego, J., Lindberg, A.A. & Levine, M.M. Age-specific prevalence of serum antibodies to the invasion plasmid and lipopolysaccharide antigens of Shigella species in Chilean and North American populations. J. Infect. Dis. 166, 158–161 (1992).

    Article  CAS  Google Scholar 

  28. Shimada, T. & Sakazaki, R. On the serology of Plesiomonas shigelloides. Jpn. J. Med. Sci. Biol. 31, 135–142 (1978).

    Article  CAS  Google Scholar 

  29. Kaminski, R.W. & Oaks, E.V. Inactivated and subunit vaccines to prevent shigellosis. Expert Rev. Vaccines 8, 1693–1704 (2009).

    Article  Google Scholar 

  30. Genobile, D. et al. An outbreak of shigellosis in a child care centre. Commun. Dis. Intell. 28, 225–229 (2004).

    Google Scholar 

  31. Lewis, H.C. et al. Outbreaks of Shigella sonnei infections in Denmark and Australia linked to consumption of imported raw baby corn. Epidemiol. Infect. 137, 326–334 (2009).

    Article  CAS  Google Scholar 

  32. Cohen, D. et al. Reduction of transmission of shigellosis by control of houseflies (Musca domestica). Lancet 337, 993–997 (1991).

    Article  CAS  Google Scholar 

  33. Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760 (2009).

    Article  CAS  Google Scholar 

  34. Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  36. Tang, J., Hanage, W.P., Fraser, C. & Corander, J. Identifying currents in the gene pool for bacterial populations using an integrative approach. PLOS Comput. Biol. 5, e1000455 (2009).

    Article  Google Scholar 

  37. Paradis, E., Claude, J. & Strimmer, K. APE: Analyses of Phylogenetics and Evolution in R language. Bioinformatics 20, 289–290 (2004).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  39. Kurtz, S. et al. Versatile and open software for comparing large genomes. Genome Biol. 5, R12 (2004).

    Article  Google Scholar 

  40. Aziz, R.K. et al. The RAST Server: rapid annotations using subsystems technology. BMC Genomics 9, 75 (2008).

    Article  Google Scholar 

Download references


We thank M. Levine (University of Maryland School of Medicine) and C. Tang (University of Oxford) for their kind gift of S. sonnei strain 53G. This work was supported by the Wellcome Trust (0689) and a Victorian Life Sciences Computation Initiative (VLSCI) grant (VR0082) on its Peak Computing Facility at the University of Melbourne (an initiative of the Victorian Government, Australia). K.E.H. was supported by a Fellowship from the National Health & Medical Research Council (NHMRC) of Australia (628930); S.B. is supported by an Oak Foundation Fellowship through Oxford University (OAKF9) and by the Li Ka Shing foundation (LG13); F.X.W. was partially funded by the Institut de Veille Sanitaire; J.Y. was supported by a UK Medical Research Council (MRC) grant (G0800173); and D.W.K. was partially supported by grant RTI05-01-01 from the Korean Ministry of Knowledge and Economy (MKE).

Author information

Authors and Affiliations



K.E.H., N.R.T., E.C.H. and A.K. analyzed the data and performed phylogenetic analysis. N.R.T., G.D., J.Y., S.B., J.J.F., K.E.H. and J.P. were involved in the study design. F.-X.W., D.J.B., J.E.C., J.Y., V.S., D.W.K., S.Y.C., S.H.K., W.D.d.S. and D.J.P. were involved in isolate collection, DNA analysis and resistance phenotyping. K.E.H., S.B., N.R.T., G.D., A.K., E.C.H. and F.-X.W. contributed to manuscript writing.

Corresponding authors

Correspondence to Kathryn E Holt or Nicholas R Thomson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary Information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Holt, K., Baker, S., Weill, FX. et al. Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe. Nat Genet 44, 1056–1059 (2012).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research