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Abstract

Listeria monocytogenes (Lm) is a major human foodborne pathogen. Numerous Lm outbreaks have been reported worldwide and associated with a high case fatality rate, reinforcing the need for strongly coordinated surveillance and outbreak control. We developed a universally applicable genome-wide strain genotyping approach and investigated the population diversity of Lm using 1,696 isolates from diverse sources and geographical locations. We define, with unprecedented precision, the population structure of Lm, demonstrate the occurrence of international circulation of strains and reveal the extent of heterogeneity in virulence and stress resistance genomic features among clinical and food isolates. Using historical isolates, we show that the evolutionary rate of Lm from lineage I and lineage II is low (2.5 × 10−7 substitutions per site per year, as inferred from the core genome) and that major sublineages (corresponding to so-called ‘epidemic clones’) are estimated to be at least 50–150 years old. This work demonstrates the urgent need to monitor Lm strains at the global level and provides the unified approach needed for global harmonization of Lm genome-based typing and population biology.

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  • 14 July 2017

    In the PDF version of this article previously published, the year of publication provided in the footer of each page and in the 'How to cite' section was erroneously given as 2017, it should have been 2016. This error has now been corrected. The HTML version of the article was not affected.

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Acknowledgements

The authors thank K. Jolley (Oxford University) for assistance with BIGSdb implementation, PulseNet International Network members for continuous surveillance and data sharing, the Genomics platform (PF1, Institut Pasteur) for assistance with sequencing, D. Mornico (Institut Pasteur) for assistance with the submission of raw data, J. Haase and M. Achtman (Environmental Research Institute, Ireland) for providing cultures of historical isolates of SL1. The authors also thank N. Tessaud-Rita, G. Vales and P. Thouvenot (National Reference Centre for Listeria, Institut Pasteur) for recovering and extracting DNA from historical isolates of SL9.

This work was supported by Institut Pasteur, INSERM, Public Health France, French government's Investissement d'Avenir program Laboratoire d'Excellence “Integrative Biology of Emerging Infectious Diseases” (grant ANR-10-LABX-62-IBEID), European Research Council, Swiss National Fund for Research and the Advanced Molecular Detection (AMD) initiative at CDC.

Author information

Affiliations

  1. National Reference Centre and World Health Organization Collaborating Center for Listeria, Institut Pasteur, 75724 Paris, France

    • Alexandra Moura
    • , Mylène M. Maury
    • , Alexandre Leclercq
    • , Hélène Bracq-Dieye
    • , Thomas Cantinelli
    • , Viviane Chenal-Francisque
    •  & Marc Lecuit
  2. Biology of Infection Unit, Institut Pasteur, 75724 Paris, France

    • Alexandra Moura
    • , Mylène M. Maury
    • , Alexandre Leclercq
    • , Hélène Bracq-Dieye
    •  & Marc Lecuit
  3. Inserm U1117, 75015 Paris, France

    • Alexandra Moura
    • , Mylène M. Maury
    •  & Marc Lecuit
  4. Microbial Evolutionary Genomics Unit, Institut Pasteur, 75724 Paris, France

    • Alexandra Moura
    • , Mylène M. Maury
    • , Elise Larsonneur
    • , Marie Touchon
    • , Eduardo P. C. Rocha
    •  & Sylvain Brisse
  5. CNRS, UMR 3525, 75015 Paris, France

    • Alexandra Moura
    • , Mylène M. Maury
    • , Marie Touchon
    • , Eduardo P. C. Rocha
    •  & Sylvain Brisse
  6. Institut Pasteur–Hub Bioinformatique et Biostatistique–C3BI, USR 3756 IP CNRS, 75724 Paris, France

    • Alexis Criscuolo
    • , Elise Larsonneur
    •  & Louis Jones
  7. Applied-Maths, 9830 Sint-Martens-Latem, Belgium

    • Hannes Pouseele
    •  & Bruno Pot
  8. Sorbonne Paris Cité, Cellule Pasteur, Paris Diderot University, 75013 Paris, France

    • Mylène M. Maury
  9. Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA

    • Cheryl Tarr
    • , Heather Carleton
    • , Lee S. Katz
    • , Steven Stroika
    • , Zuzana Kucerova
    •  & Peter Gerner-Smidt
  10. Statens Serum Institut, 2300 Copenhagen, Denmark

    • Jonas T. Björkman
    •  & Eva M. Nielsen
  11. Public Health England, London NW9 5EQ, UK

    • Timothy Dallman
    •  & Kathie Grant
  12. Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada

    • Aleisha Reimer
    • , Matthew Walker
    •  & Celine Nadon
  13. Pasteur International Bioresources network (PIBnet), Mutualized Microbiology Platform (P2M), Institut Pasteur, 75724 Paris, France

    • Vincent Enouf
  14. CNRS, UMS 3601 IFB-Core, 91198 Gif-sur-Yvette, France

    • Elise Larsonneur
  15. Public Health France, 94415 Saint-Maurice, France

    • Mathieu Tourdjman
  16. Sorbonne Paris Cité, Institut Imagine, 75006 Paris, Necker-Enfants Malades University Hospital, Division of Infectious Diseases and Tropical Medicine, APHP, Paris Descartes University, 75015 Paris, France

    • Marc Lecuit

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Contributions

This study was designed by S.B., M.L., P.G.-S. and B.P. Selection of isolates was carried out by E.M.N., C.N., V.C.-F., A.L., A.R., K.G., T.D. and L.S.K. DNA preparation and sequencing was performed by H.B.-D., V.C.-F., A.L., C.T., H.C., S.S., Z.K., J.T.B., A.R., C.N., K.G., M.W. and V.E. PFGE analysis was performed by H.B.-D., V.C.-F., A.L. and A.M. Sequence analysis was carried out by A.M., H.P., T.C., L.S.K., H.C. and J.T.B. Definition of core genome was done by M.M.M., E.P.C.R., M.Touc. Validation and reproducibility of cgMLST loci was performed by A.M., H.P. and E.L. Phylogenetic and clustering analyses were carried out by A.M. and A.C. Online database implementation was done by L.J., A.M. and S.B. Epidemiological data analysis was performed by M.Tour. A.L., A.M., T.D., K.G., E.M.N. and C.T. A.M. and S.B. wrote the manuscript, with contributions and comments from all authors.

Competing interests

H.P. and B.P. are co-developers of the BioNumerics software mentioned in the manuscript. The remaining authors declare no competing interests.

Corresponding authors

Correspondence to Marc Lecuit or Sylvain Brisse.

Supplementary information

PDF files

  1. 1.

    Supplementary information

    Legends for Supplementary Tables 1–8, Supplementary Text, Supplementary Figures 1–11, Supplementary References

Excel files

  1. 1.

    Supplementary Table 1

    Characteristics of the 1,696 Listeria monocytogenes isolates used in this study.

  2. 2.

    Supplementary Table 2

    Loci (n = 43) excluded from the initial set of 1,791 core genes.

  3. 3.

    Supplementary Table 3

    Characteristics of the 1,748 loci included in the cgMLST scheme.

  4. 4.

    Supplementary Table 4

    Prevalence of sublineages (SL) identified in this study using cgMLST and correspondence with clonal complexes (CC) and sequence types (ST) defined based on conventional MLST

  5. 5.

    Supplementary Table 5

    Historical SL1 and SL9 isolates used for temporal analyses.

  6. 6.

    Supplementary Table 6

    International clusters of isolates belonging to the same cgMLST type.

  7. 7.

    Supplementary Table 7

    Detection of recombination regions within major sublineages.

  8. 8.

    Supplementary Table 8

    Frameshifts and mutations identified in this study leading to premature stop codons (PMSC) in inlA gene.

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DOI

https://doi.org/10.1038/nmicrobiol.2016.185

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