• A Corrigendum to this article was published on 30 March 2017
  • An Erratum to this article was published on 26 May 2017

This article has been updated


Microbial pathogenesis studies are typically performed with reference strains, thereby overlooking within-species heterogeneity in microbial virulence. Here we integrated human epidemiological and clinical data with bacterial population genomics to harness the biodiversity of the model foodborne pathogen Listeria monocytogenes and decipher the basis of its neural and placental tropisms. Taking advantage of the clonal structure of this bacterial species, we identify clones epidemiologically associated either with food or with human central nervous system (CNS) or maternal-neonatal (MN) listeriosis. The latter clones are also most prevalent in patients without immunosuppressive comorbidities. Strikingly, CNS- and MN-associated clones are hypervirulent in a humanized mouse model of listeriosis. By integrating epidemiological data and comparative genomics, we have uncovered multiple new putative virulence factors and demonstrate experimentally the contribution of the first gene cluster mediating L. monocytogenes neural and placental tropisms. This study illustrates the exceptional power in harnessing microbial biodiversity to identify clinically relevant microbial virulence attributes.

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Change history

  • 06 March 2017

    In the version of this article initially published, in Figure 2b, in the panel called "CNS infections" the bar of CC3 should have been represented in red and the one of CC121 should have been represented in blue. The errors have been corrected in the HTML and PDF versions of the article.

  • 06 March 2017

    In the version of this article initially published, the titles of the x axes in Figure 5b and 5c should have been “Brain/blood CFU ratio” instead of "Blood/brain CFU ratio," and the title of the z axis in Figure 2c should have been "% of isolates" instead of "Number of isolates." The errors have been corrected in the HTML and PDF versions of the article.


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We thank C. Soto Alvarez, G. Pontdeme, T. Cantinelli and L. Diancourt for their contributions to MLST data production and analysis, and S. Roche for providing low-virulence strains for genome sequencing. We also thank D. Mornico (Center of Bioinformatics, Biostatistics and Integrative Biology of the Institut Pasteur) for his help with the submission of genome reads and assemblies. This study was funded by the Institut Pasteur, INSERM, from the French government's Investissement d'Avenir program, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant ANR-10-LABX-62-IBEID), the European Research Council (ERC), ERANET Proantilis, the Programme Hospitalier de Recherche Clinique MONALISA and the Programme de Recherche Translationnelle (PTR) ANSES–Institut Pasteur. Listeriosis surveillance in France is funded by the Institut de Veille Sanitaire (InVS) and the Institut Pasteur.

Author information

Author notes

    • Mylène M Maury
    •  & Yu-Huan Tsai

    These authors contributed equally to this work.

    • Sylvain Brisse
    •  & Marc Lecuit

    These authors jointly supervised this work.


  1. Institut Pasteur, Microbial Evolutionary Genomics Unit, Paris, France.

    • Mylène M Maury
    • , Marie Touchon
    • , Eduardo P C Rocha
    •  & Sylvain Brisse
  2. CNRS, UMR 3525, Paris, France.

    • Mylène M Maury
    • , Marie Touchon
    • , Eduardo P C Rocha
    •  & Sylvain Brisse
  3. Paris Diderot University, Sorbonne Paris Cité, Cellule Pasteur, Paris, France.

    • Mylène M Maury
  4. Institut Pasteur, Biology of Infection Unit, Paris, France.

    • Yu-Huan Tsai
    • , Caroline Charlier
    • , Viviane Chenal-Francisque
    • , Alexandre Leclercq
    • , Charlotte Gaultier
    • , Olivier Disson
    •  & Marc Lecuit
  5. INSERM Unit 1117, Paris, France.

    • Yu-Huan Tsai
    • , Caroline Charlier
    • , Charlotte Gaultier
    • , Olivier Disson
    •  & Marc Lecuit
  6. National Reference Centre for Listeria, Paris, France.

    • Caroline Charlier
    • , Viviane Chenal-Francisque
    • , Alexandre Leclercq
    •  & Marc Lecuit
  7. World Health Organization Collaborating Center for Listeria, Paris, France.

    • Caroline Charlier
    • , Viviane Chenal-Francisque
    • , Alexandre Leclercq
    •  & Marc Lecuit
  8. Paris Descartes University, Sorbonne Paris Cité, Institut Imagine, Necker–Enfants Malades University Hospital, Division of Infectious Diseases and Tropical Medicine, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France.

    • Caroline Charlier
    •  & Marc Lecuit
  9. Institut Pasteur, Center of Bioinformatics, Biostatistics and Integrative Biology, Paris, France.

    • Alexis Criscuolo
  10. Paris-Est University, ANSES (Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail), Food Safety Laboratory, Maisons-Alfort, France.

    • Sophie Roussel
    •  & Anne Brisabois


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M.L. and S.B. conceived, supervised and directed the project. L. monocytogenes isolates were collected and characterized by A.L. in the context of French National Reference Center for Listeria activities, with the help of V.C.-F., as well as A.B. and S.R. Methods for clone identification were developed by M.M.M. and S.B. Epidemiological analyses were performed by M.M.M. and S.B. Clinical data collection and analysis was conducted by C.C. and M.L. Statistical analyses were performed by M.M.M. and E.P.C.R. Comparative genomics analyses were performed by M.M.M., M.T. and E.P.C.R. Phylogenetic analyses were performed by M.M.M., A.C. and M.T. Y.-H.T. generated mutant CC4 strains. In vivo experiments were performed by Y.-H.T., O.D. and C.G. M.M.M., S.B. and M.L. wrote the manuscript, with contributions from Y.-H.T., C.C., A.L., M.T. and E.P.C.R.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Sylvain Brisse or Marc Lecuit.

Integrated supplementary information

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–7 and Supplementary Note.

Excel files

  1. 1.

    Supplementary Table 1

    Distribution of genotypic categories in food and clinical sources.

  2. 2.

    Supplementary Table 2

    Distribution of genotypic categories in bacteremia, CNS and MN infections.

  3. 3.

    Supplementary Table 3

    Bacterial strains used for in vivo tests.

  4. 4.

    Supplementary Table 4

    Stepwise multiple regression of the parameters recorded during the in vivo experiments on the clinical frequencies of clones.

  5. 5.

    Supplementary Table 5

    Genomes used in this study.

  6. 6.

    Supplementary Table 6

    Gene families of the core genome.

  7. 7.

    Supplementary Table 7

    Virulence gene products shown in Supplementary Figure 5.

  8. 8.

    Supplementary Table 8

    Pan-genome of the 104 genomes.

  9. 9.

    Supplementary Table 9

    Correlation of the pattern of presence/absence of gene families of the pan-genome with the clinical frequency of clones.

  10. 10.

    Supplementary Table 10

    Primers used for CC4-specific PTS mutagenesis.

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