FN Archimer Export Format PT J TI Functional Diversification of Oyster Big Defensins Generates Antimicrobial Specificity and Synergy against Members of the Microbiota BT AF De San Nicolas, Noémie Asokan, Aromal Rosa, Rafael D. Voisin, Sébastien N. TRAVERS, Agnes 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 GARZON, Delphine AS 1:9;2:2;3:3;4:4;5:1;6:3;7:9;8:1;9:1,5;10:6;11:9;12:10;13:9;14:9;15:2;16:2,7;17:2;18:2;19:4,8;20:1;21:10; FF 1:;2:;3:;4:;5:PDG-RBE-IHPE;6:;7:;8:PDG-RBE-IHPE;9:PDG-RBE-RMPF;10:PDG-RBE-PFOM-LPI;11:;12:;13:PDG-RBE-IHPE;14:PDG-RBE-IHPE;15:;16:;17:;18:;19:;20:PDG-RBE-IHPE;21:; C1 IHPE, Univ. Montpellier, CNRS, Ifremer, Univ. Perpignan Via Domitia, 34090 Montpellier, France Centre de Biophysique Moléculaire UPR4301 CNRS, 45071 Orléans, France Laboratory of Immunology Applied to Aquaculture, Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, 88040-900 Florianópolis, Santa Catarina, Brazil Plateforme BioPark d’Archamps, Archparc, 74160 Archamps, France Ifremer, IRD, ILM, Université de Polynésie Française, UMR EIO, 98179 Vairao, French Polynesia Ifremer, CNRS, IRD, Ifremer, LEMAR UMR 6539 Université de Bretagne Occidentale, 29840 Argenton-en-Landunvez, France UFR ST, Université d’Orléans, 45067 Orléans, France CR UGA, IAB, INSERM U1209, CNRS UMR5309, 74160 La Tronche-Archamps, France IHPE, Univ. Montpellier, CNRS, Ifremer, Univ. Perpignan Via Domitia, 34090 Montpellier, France IHPE, Univ. Montpellier, CNRS, Ifremer, Univ. Perpignan Via Domitia, 34090 Montpellier, France C2 IFREMER, FRANCE CNRS, FRANCE UNIV FED SANTA CATARINA, BRAZIL PLATEFORME BIOPARK D’ARCHAMPS, FRANCE IFREMER, FRANCE IFREMER, FRANCE UNIV ORLEANS, FRANCE CNRS, FRANCE UNIV MONTPELLIER, FRANCE CNRS, FRANCE SI MONTPELLIER TAHITI ARGENTON SE PDG-RBE-IHPE PDG-RBE-RMPF PDG-RBE-PFOM-LPI UM LEMAR IHPE EIO IN WOS Ifremer UMR WOS Cotutelle UMR DOAJ copubli-france copubli-univ-france copubli-int-hors-europe copubli-sud IF 5.4 TC 3 UR https://archimer.ifremer.fr/doc/00807/91932/97892.pdf https://archimer.ifremer.fr/doc/00807/91932/97893.zip LA English DT Article DE ;antibacterial peptide;beta defensin;diversity;evolution;microbiome;invertebrate;mollusk AB 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. PY 2022 PD DEC SO Marine Drugs SN 1660-3397 PU MDPI AG VL 20 IS 12 UT 000902639900001 DI 10.3390/md20120745 ID 91932 ER EF