Abstract

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.

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References

  1. 1.

    , & 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).

  2. 2.

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

  3. 3.

    , , & Inoculum size in shigellosis and implications for expected mode of transmission. J. Infect. Dis. 159, 1126–1128 (1989).

  4. 4.

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

  5. 5.

    , , & Is protection against shigellosis induced by natural infection with Plesiomonas shigelloides? Lancet 343, 1413–1415 (1994).

  6. 6.

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

  7. 7.

    , & 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).

  8. 8.

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

  9. 9.

    , , & rRNA gene restriction patterns and biotypes of Shigella sonnei. Epidemiol. Infect. 110, 23–30 (1993).

  10. 10.

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

  11. 11.

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

  12. 12.

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

  13. 13.

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

  14. 14.

    , & Correlating viral phenotypes with phylogeny: accounting for phylogenetic uncertainty. Infect. Genet. Evol. 8, 239–246 (2008).

  15. 15.

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

  16. 16.

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

  17. 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. 18.

    , , & Antibiotic therapy for Shigella dysentery. Cochrane Database Syst. Rev. CD006784 (2010).

  19. 19.

    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).

  20. 20.

    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).

  21. 21.

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

  22. 22.

    , , & Acanthamoeba castellanii an environmental host for Shigella dysenteriae and Shigella sonnei. Arch. Microbiol. 191, 83–88 (2009).

  23. 23.

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

  24. 24.

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

  25. 25.

    , & 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).

  26. 26.

    , & Shigella sonnei plasmids: evidence that a large plasmid is necessary for virulence. Infect. Immun. 34, 75–83 (1981).

  27. 27.

    , , , & 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).

  28. 28.

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

  29. 29.

    & Inactivated and subunit vaccines to prevent shigellosis. Expert Rev. Vaccines 8, 1693–1704 (2009).

  30. 30.

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

  31. 31.

    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).

  32. 32.

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

  33. 33.

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

  34. 34.

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

  35. 35.

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

  36. 36.

    , , & Identifying currents in the gene pool for bacterial populations using an integrative approach. PLOS Comput. Biol. 5, e1000455 (2009).

  37. 37.

    , & APE: Analyses of Phylogenetics and Evolution in R language. Bioinformatics 20, 289–290 (2004).

  38. 38.

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

  39. 39.

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

  40. 40.

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

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Acknowledgements

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

Affiliations

  1. Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia.

    • Kathryn E Holt
  2. The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.

    • Stephen Baker
    •  & Jeremy J Farrar
  3. Unité des Bactéries Pathogènes Entériques, Institut Pasteur, Paris, France.

    • François-Xavier Weill
  4. Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.

    • Edward C Holmes
    •  & Andrew Kitchen
  5. Fogarty International Center, US National Institutes of Health, Bethesda, Maryland, USA.

    • Edward C Holmes
  6. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.

    • Jun Yu
    •  & Vartul Sangal
  7. Scottish Salmonella, Shigella and Clostridium difficile Reference Laboratory, Stobhill Hospital, Glasgow, UK.

    • Derek J Brown
    •  & John E Coia
  8. Molecular Biology Laboratory, International Vaccine Institute (IVI), Seoul, Republic of Korea.

    • Dong Wook Kim
    • , Seon Young Choi
    •  & Su Hee Kim
  9. Department of Pharmacy, College of Pharmacy, Hanyang University Ansan, Kyeonggi-do, Republic of Korea.

    • Dong Wook Kim
  10. Department of Genetics, Evolution and Bioagents, Biology Institute, Campinas State University (UNICAMP), Campinas, Brazil.

    • Wanderley D da Silveira
  11. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

    • Derek J Pickard
    • , Julian Parkhill
    • , Gordon Dougan
    •  & Nicholas R Thomson

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Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Kathryn E Holt or Nicholas R Thomson.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–6, Supplementary Tables 2 and 3 and Supplementary Note

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    Supplementary Table 1

    Details of Shigella sonnei isolates used in this study.

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DOI

https://doi.org/10.1038/ng.2369

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