Functional Diversification of Oyster Big Defensins Generates Antimicrobial Specificity and Synergy against Members of the Microbiota

International audience Big defensins are two-domain antimicrobial peptides (AMPs) that have highly diversified in mollusks. Cg-BigDefs are expressed by immune cells in the oyster Crassostrea gigas, and their expression is dampened during the Pacific Oyster Mortality Syndrome (POMS), which evolves to...

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Published in:Marine Drugs
Main Authors: de San Nicolas, Noémie, Asokan, Aromal, Rosa, Rafael, D, Voisin, Sébastien, N, Travers, Marie-Agnès, Rocha, Gustavo, Dantan, Luc, Dorant, Yann, Mitta, Guillaume, Petton, Bruno, Charrière, Guillaume, M, Escoubas, Jean-Michel, Boulo, Viviane, Pouzadoux, Juliette, Meudal, Hervé, Loth, Karine, Aucagne, Vincent, Delmas, Agnès, F, Bulet, Philippe, Montagnani, Caroline, Destoumieux-Garzón, Delphine
Other Authors: Interactions Hôtes-Pathogènes-Environnements (IHPE), Université de Perpignan Via Domitia (UPVD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS), Universidade Federal de Santa Catarina = Federal University of Santa Catarina Florianópolis (UFSC), Ecosystèmes Insulaires Océaniens (UMR 241) (EIO), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de la Polynésie Française (UPF)-Institut Louis Malardé Papeete (ILM), Institut de Recherche pour le Développement (IRD), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ecologie marine tropicale des océans Pacifique et Indien (ENTROPIE Nouvelle-Calédonie ), Institut de Recherche pour le Développement (IRD Nouvelle-Calédonie )-Délégation Ifremer de Nouvelle-Calédonie, Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de la Nouvelle-Calédonie (UNC), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), ANR-19-CE20-0004,DECICOMP,Déchiffrer toute la complexité du syndrome de mortalité des huîtres du Pacifique pour modéliser le risque épidémiologique.(2019), ANR-19-CE18-0025,MOSAR-DEF,Conception d'antimicrobiens actifs en milieu salin inspirée par la biodivesité marine.(2019)
Format: Article in Journal/Newspaper
Language:English
Published: HAL CCSD 2022
Subjects:
Online Access:https://hal.science/hal-04246173
https://hal.science/hal-04246173/document
https://hal.science/hal-04246173/file/marinedrugs-20-00745.pdf
https://doi.org/10.3390/md20120745
Description
Summary:International audience Big defensins are two-domain antimicrobial peptides (AMPs) that have highly diversified in mollusks. Cg-BigDefs are expressed by immune cells in the oyster Crassostrea gigas, and their expression is dampened during the Pacific Oyster Mortality Syndrome (POMS), which evolves toward fatal bacteremia. We evaluated whether Cg-BigDefs contribute to the control of oyster-associated microbial communities. Two Cg-BigDefs that are representative of molecular diversity within the peptide family, namely Cg-BigDef1 and Cg-BigDef5, were characterized by gene cloning and synthesized by solid-phase peptide synthesis and native chemical ligation. Synthetic peptides were tested for antibacterial activity against a collection of culturable bacteria belonging to the oyster microbiota, characterized by 16S sequencing and MALDI Biotyping. We first tested the potential of Cg-BigDefs to control the oyster microbiota by injecting synthetic Cg-BigDef1 into oyster tissues and analyzing microbiota dynamics over 24 h by 16S metabarcoding. Cg-BigDef1 induced a significant shift in oyster microbiota β-diversity after 6 h and 24 h, prompting us to investigate antimicrobial activities in vitro against members of the oyster microbiota. Both Cg-BigDef1 and Cg-BigDef5 were active at a high salt concentration (400 mM NaCl) and showed broad spectra of activity against bacteria associated with C. gigas pathologies. Antimicrobial specificity was observed for both molecules at an intra- and inter-genera level. Remarkably, antimicrobial spectra of Cg-BigDef1 and Cg-BigDef5 were complementary, and peptides acted synergistically. Overall, we found that primary sequence diversification of Cg-BigDefs has generated specificity and synergy and extended the spectrum of activity of this peptide family.