1. Distinct virulence ranges for infection of mice by Bordetella pertussis revealed by engineering of the sensor-kinase BvgS
- Author
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Lesne, Elodie, Coutte, Loic, Solans, Luis, Slupek, Stephanie, Debrie, Anne-Sophie, Dhennin, Véronique, Froguel, Philippe, Hot, David, Locht, Camille, Antoine, Rudy, Jacob-Dubuisson, Françoise, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), and Jacob-Dubuisson, Françoise
- Subjects
Whooping Cough ,Bordetella ,Molecular biology ,[SDV]Life Sciences [q-bio] ,Gene Expression ,lcsh:Medicine ,Protein Engineering ,Pathology and Laboratory Medicine ,Bordetella pertussis ,DISEASE ,ACTIVATION ,Mice ,Sequencing techniques ,Medicine and Health Sciences ,lcsh:Science ,Lung ,Virulence ,VENUS FLYTRAP ,RNA sequencing ,Animal Models ,Genomics ,INTERMEDIATE PHASE ,Bacterial Pathogens ,[SDV] Life Sciences [q-bio] ,Multidisciplinary Sciences ,RECEPTORS ,Experimental Organism Systems ,Medical Microbiology ,Host-Pathogen Interactions ,BACTERIA ,Science & Technology - Other Topics ,Anatomy ,Pathogens ,Transcriptome Analysis ,Research Article ,RESPIRATORY-INFECTION ,Virulence Factors ,General Science & Technology ,Mouse Models ,Nose ,Research and Analysis Methods ,Microbiology ,TRANSDUCTION ,Model Organisms ,Bacterial Proteins ,MD Multidisciplinary ,Genetics ,Animals ,Animal Models of Disease ,Microbial Pathogens ,Science & Technology ,Sequence Analysis, RNA ,MUTATIONS ,Gene Expression Profiling ,lcsh:R ,Organisms ,Biology and Life Sciences ,Computational Biology ,Gene Expression Regulation, Bacterial ,Genome Analysis ,GENE ,Disease Models, Animal ,Animal Models of Infection ,Molecular biology techniques ,Face ,Mutation ,Animal Studies ,lcsh:Q ,Head ,Transcription Factors - Abstract
International audience; The whooping cough agent Bordetella pertussis coordinately regulates the expression of its virulence factors with the two-component system BvgAS. In laboratory conditions, specific chemical modulators are used to trigger phenotypic modulation of B. pertussis from its default virulent Bvg + phase to avirulent Bvg-or intermediate Bvg i phases, in which no viru-lence factors or only a subset of them are produced, respectively. Whether phenotypic modulation occurs in the host remains unknown. In this work, recombinant B. pertussis strains harboring BvgS variants were tested in a mouse model of infection and analyzed using tran-scriptomic approaches. Recombinant BP-Bvg Δ65, which is in the Bvg i phase by default and can be up-modulated to the Bvg + phase in vitro, could colonize the mouse nose but was rapidly cleared from the lungs, while Bvg +-phase strains colonized both organs for up to four weeks. These results indicated that phenotypic modulation, which might have restored the full virulence capability of BP-Bvg Δ65, does not occur in mice or is temporally or spatially restricted and has no effect in those conditions. Transcriptomic analyses of this and other recombinant Bvg i and Bvg +-phase strains revealed that two distinct ranges of virulence gene expression allow colonization of the mouse nose and lungs, respectively. We also showed that a recombinant strain expressing moderately lower levels of the virulence genes than its wild type parent was as efficient at colonizing both organs. Altogether, genetic modifications of BvgS generate a range of phenotypic phases, which are useful tools to decipher host-pathogen interactions.
- Published
- 2018