title: Copper homeostasis at the host vibrio interface: lessons from intracellular vibrio transcriptomics.
abstract: Recent studies revealed that several vibrio species have evolved the capacity to survive inside host cells. However, it is still often ignored if intracellular stages are required for pathogenicity. Virulence of Vibrio tasmaniensis LGP32, a strain pathogenic for Crassostrea gigas oysters, depends on entry into hemocytes, the oyster immune cells. We investigated here the mechanisms of LGP32 intracellular survival and their consequences on the host-pathogen interaction. Entry and survival inside hemocytes were required for LGP32-driven cytolysis of hemocytes, both in vivo and in vitro. LGP32 intracellular stages showed a profound boost in metabolic activity and a major transcription of antioxidant and copper detoxification genes, as revealed by RNA sequencing. LGP32 isogenic mutants showed that resistance to oxidative stress and copper efflux are two main functions required for vibrio intracellular stages and cytotoxicity to hemocytes. Copper efflux was also essential for host colonization and virulence in vivo. Altogether, our results identify copper resistance as a major mechanism to resist killing by phagocytes, induce cytolysis of immune cells and colonize oysters. Selection of such resistance traits could arise from vibrio interactions with copper-rich environmental niches including marine invertebrates, which favour the emergence of pathogenic vibrios resistant to intraphagosomal killing across animal species.
authors.affiliation: Interactions Hôtes-Pathogènes-Environnements (IHPE), UMR 5244, CNRS, Ifremer, Université de Perpignan Via Domitia, Université de Montpellier, Montpellier, 34095, France.
authors.forename: Audrey S
authors.initials: AS
authors.lastname: Vanhove
authors.affiliation: Interactions Hôtes-Pathogènes-Environnements (IHPE), UMR 5244, CNRS, Ifremer, Université de Perpignan Via Domitia, Université de Montpellier, Montpellier, 34095, France.
authors.forename: Tristan P
authors.initials: TP
authors.lastname: Rubio
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Orsay Cedex, 91405, France.
authors.forename: An N
authors.initials: AN
authors.lastname: Nguyen
authors.affiliation: Unité Physiologie Fonctionnelle des Organismes Marins, Ifremer, ZI de la Pointe du Diable, CS 10070, Plouzané, 29280, France.|UPMC Paris 06, CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, Sorbonne Université, CS 90074, Roscoff cedex, 29688, France.
authors.forename: Astrid
authors.initials: A
authors.lastname: Lemire
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Direction des Sciences du Vivant (DSV), Institut de Génomique (IG), Génoscope, Evry cedex, 91057, France.|CNRS, UMR 8030, Laboratoire d'Analyse Bioinformatiques en Génomique et Métabolisme (LABGeM), Evry cedex, 91057, France.
authors.forename: David
authors.initials: D
authors.lastname: Roche
authors.affiliation: Interactions Hôtes-Pathogènes-Environnements (IHPE), UMR 5244, CNRS, Ifremer, Université de Perpignan Via Domitia, Université de Montpellier, Montpellier, 34095, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Nicod
authors.affiliation: Interactions Hôtes-Pathogènes-Environnements (IHPE), UMR 5244, CNRS, Ifremer, Université de Perpignan Via Domitia, Université de Montpellier, Montpellier, 34095, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Vergnes
authors.affiliation: Interactions Hôtes-Pathogènes-Environnements (IHPE), UMR 5244, CNRS, Ifremer, Université de Perpignan Via Domitia, Université de Montpellier, Montpellier, 34095, France.
authors.forename: Aurore C
authors.initials: AC
authors.lastname: Poirier
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Orsay Cedex, 91405, France.
authors.forename: Elena
authors.initials: E
authors.lastname: Disconzi
authors.affiliation: Interactions Hôtes-Pathogènes-Environnements (IHPE), UMR 5244, CNRS, Ifremer, Université de Perpignan Via Domitia, Université de Montpellier, Montpellier, 34095, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Bachère
authors.affiliation: Unité Physiologie Fonctionnelle des Organismes Marins, Ifremer, ZI de la Pointe du Diable, CS 10070, Plouzané, 29280, France.|UPMC Paris 06, CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, Sorbonne Université, CS 90074, Roscoff cedex, 29688, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Le Roux
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Orsay Cedex, 91405, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Jacq
authors.affiliation: Interactions Hôtes-Pathogènes-Environnements (IHPE), UMR 5244, CNRS, Ifremer, Université de Perpignan Via Domitia, Université de Montpellier, Montpellier, 34095, France.
authors.forename: Guillaume M
authors.initials: GM
authors.lastname: Charrière
authors.affiliation: Interactions Hôtes-Pathogènes-Environnements (IHPE), UMR 5244, CNRS, Ifremer, Université de Perpignan Via Domitia, Université de Montpellier, Montpellier, 34095, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Destoumieux-Garzón
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D003300:Copper / Q000378:metabolism*; D049896:Crassostrea / Q000382:microbiology*; D003593:Cytoplasm; D006434:Hemocytes / Q000276:immunology / Q000382:microbiology*; D006706:Homeostasis; D054884:Host-Pathogen Interactions; D017423:Sequence Analysis, RNA; D012758:Shellfish / Q000382:microbiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014733:Vibrio / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; C071263:CopA protein, Bacteria; D003300:Copper; C095500:SodA protein, Bacteria; D013482:Superoxide Dismutase