title: Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity.
abstract: 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.
authors.affiliation: Institut Pasteur, Microbial Evolutionary Genomics Unit, 75015, Paris, France.|CNRS, UMR 3525, 75015, Paris, France.|Paris Diderot University, Sorbonne Paris Cité, Cellule Pasteur, rue du Dr Roux, 75015 Paris, France.
authors.forename: Mylène M
authors.initials: MM
authors.lastname: Maury
authors.affiliation: Institut Pasteur, Biology of Infection Unit, Paris, France.|Inserm Unit 1117, Paris, France.
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Tsai
authors.affiliation: Institut Pasteur, Biology of Infection Unit, Paris, France.|Inserm Unit 1117, Paris, France.|National Reference Centre for Listeria, Paris, France.|WHO Collaborating Center for Listeria, Paris, France.|Paris Descartes University, Sorbonne Paris Cité, Institut Imagine, Necker-Enfants Malades University Hospital, Division of Infectious Diseases and Tropical Medicine, APHP, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Charlier
authors.affiliation: Institut Pasteur, Microbial Evolutionary Genomics Unit, 75015, Paris, France.|CNRS, UMR 3525, 75015, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Touchon
authors.affiliation: Institut Pasteur, Biology of Infection Unit, Paris, France.|National Reference Centre for Listeria, Paris, France.|WHO Collaborating Center for Listeria, Paris, France.
authors.forename: Viviane
authors.initials: V
authors.lastname: Chenal-Francisque
authors.affiliation: Institut Pasteur, Biology of Infection Unit, Paris, France.|National Reference Centre for Listeria, Paris, France.|WHO Collaborating Center for Listeria, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Leclercq
authors.affiliation: Institut Pasteur, Center of Bioinformatics, Biostatistics and Integrative Biology Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Criscuolo
authors.affiliation: Institut Pasteur, Biology of Infection Unit, Paris, France.|Inserm Unit 1117, Paris, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gaultier
authors.affiliation: Paris-Est University, ANSES, Food Safety Laboratory, F-94701, Maisons-Alfort, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Roussel
authors.affiliation: Paris-Est University, ANSES, Food Safety Laboratory, F-94701, Maisons-Alfort, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Brisabois
authors.affiliation: Institut Pasteur, Biology of Infection Unit, Paris, France.|Inserm Unit 1117, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Disson
authors.affiliation: Institut Pasteur, Microbial Evolutionary Genomics Unit, 75015, Paris, France.|CNRS, UMR 3525, 75015, Paris, France.
authors.forename: Eduardo P C
authors.initials: EPC
authors.lastname: Rocha
authors.affiliation: Institut Pasteur, Microbial Evolutionary Genomics Unit, 75015, Paris, France.|CNRS, UMR 3525, 75015, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brisse
authors.affiliation: Institut Pasteur, Biology of Infection Unit, Paris, France.|Inserm Unit 1117, Paris, France.|National Reference Centre for Listeria, Paris, France.|WHO Collaborating Center for Listeria, Paris, France.|Paris Descartes University, Sorbonne Paris Cité, Institut Imagine, Necker-Enfants Malades University Hospital, Division of Infectious Diseases and Tropical Medicine, APHP, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lecuit
mesh_terms: D000818:Animals; D044822:Biodiversity; D002490:Central Nervous System / Q000382:microbiology / Q000473:pathology; D023281:Genomics; D006801:Humans; D008089:Listeria monocytogenes / Q000235:genetics* / Q000472:pathogenicity; D008088:Listeriosis / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology; D051379:Mice; D010802:Phylogeny
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