Spontaneous Loss of Virulence in Natural Populations of Listeria monocytogenes
| Autor: | Mariela Scortti, Alexandra Moura, Lei Han, Guillaume Vales, Alexandre Leclercq, Olivier Disson, Marc Lecuit, Hélène Bracq-Dieye, Mylène M. Maury, Edith Gouin, José A. Vázquez-Boland, Viviane Chenal-Francisque |
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| Přispěvatelé: | Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Edinburgh, Biologie des Infections - Biology of Infection, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Work in M.L.'s laboratory was supported by Institut Pasteur, Inserm, LabEx IBEID, the European Research Council, and Santé Publique France. Work in J.A.V.-B.'s laboratory was supported by the Wellcome Trust (program grant WT074020MA) and partially by core Roslin Institute funding from BBSRC (BB/J004227/1), We acknowledge Anne Morvan, Thomas Cantinelli, Nathalie Tessaud-Rita and Laetitia Bellon for their help in strain collection and isolation at the National Reference Centre for Listeria. We thank Pascale Cossart for providing antibodies against LLO and the Institut Pasteur P2M platform for genome sequencing., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), DIAKITE, andrée, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), Centre National de Référence Listeria - Biologie des Infections (CNRL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Institut des Maladies Génétiques Imagine [Paris], ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Erythrocytes MESH: Selection Genetic Mutant MESH: Heat-Shock Proteins MESH: Virulence medicine.disease_cause MESH: Listeria monocytogenes Severity of Illness Index MESH: Recombinant Proteins Hemolysin Proteins Mice [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Listeriosis MESH: Animals Cloning Molecular MESH: Phylogeny Pathogen MESH: Bacterial Proteins Heat-Shock Proteins Phylogeny Mice Inbred BALB C MESH: Gene Expression Regulation Bacterial [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology MESH: Erythrocytes Listeriolysin O Biological Evolution spontaneous mutations MESH: Amino Acid Substitution MESH: Hemolysis Recombinant Proteins Infectious Diseases [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology MESH: Hemolysin Proteins [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Peptide Termination Factors Peptide Termination Factors Transposable element MESH: Mutation Bacterial Toxins 030106 microbiology Immunology MESH: Mice Inbred BALB C Virulence Molecular Genomics MESH: Biological Evolution Biology Microbiology Frameshift mutation 03 medical and health sciences Bacterial Proteins Listeria monocytogenes MESH: Severity of Illness Index medicine genomics Animals Humans MESH: Cloning Molecular Selection Genetic [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology Gene MESH: Mice MESH: Humans Gene Expression Regulation Bacterial biochemical phenomena metabolism and nutrition [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology virulence Amino Acid Substitution MESH: Bacterial Toxins MESH: Listeriosis Mutation Parasitology [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology hemolysis [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Infection and Immunity Infection and Immunity, 2017, 85 (11), pp.e00541-17. ⟨10.1128/IAI.00541-17⟩ Infection and Immunity, American Society for Microbiology, 2017, 85 (11), pp.e00541-17. ⟨10.1128/IAI.00541-17⟩ |
| ISSN: | 0019-9567 1098-5522 |
| DOI: | 10.1128/IAI.00541-17⟩ |
| Popis: | The pathogenesis of Listeria monocytogenes depends on the ability of this bacterium to escape from the phagosome of the host cells via the action of the pore-forming toxin listeriolysin O (LLO). Expression of the LLO-encoding gene ( hly ) requires the transcriptional activator PrfA, and both hly and prfA genes are essential for L. monocytogenes virulence. Here, we used the hemolytic activity of LLO as a phenotypic marker to screen for spontaneous virulence-attenuating mutations in L. monocytogenes . Sixty nonhemolytic isolates were identified among a collection of 57,820 confirmed L. monocytogenes strains isolated from a variety of sources (0.1%). In most cases (56/60; 93.3%), the nonhemolytic phenotype resulted from nonsense, missense, or frameshift mutations in prfA . Five strains carried hly mutations leading to a single amino acid substitution (G299V) or a premature stop codon causing strong virulence attenuation in mice. In one strain, both hly and gshF (encoding a glutathione synthase required for full PrfA activity) were missing due to genomic rearrangements likely caused by a transposable element. The PrfA/LLO loss-of-function (PrfA − /LLO − ) mutants belonged to phylogenetically diverse clades of L. monocytogenes , and most were identified among nonclinical strains (57/60). Consistent with the rare occurrence of loss-of-virulence mutations, we show that prfA and hly are under purifying selection. Although occurring at a low frequency, PrfA − /LLO − mutational events in L. monocytogenes lead to niche restriction and open an evolutionary path for obligate saprophytism in this facultative intracellular pathogen. |
| Databáze: | OpenAIRE |
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