title: The targeted recognition of Lactococcus lactis phages to their polysaccharide receptors.
abstract: Each phage infects a limited number of bacterial strains through highly specific interactions of the receptor-binding protein (RBP) at the tip of phage tail and the receptor at the bacterial surface. Lactococcus lactis is covered with a thin polysaccharide pellicle (hexasaccharide repeating units), which is used by a subgroup of phages as a receptor. Using L. lactis and phage 1358 as a model, we investigated the interaction between the phage RBP and the pellicle hexasaccharide of the host strain. A core trisaccharide (TriS), derived from the pellicle hexasaccharide repeating unit, was chemically synthesised, and the crystal structure of the RBP/TriS complex was determined. This provided unprecedented structural details of RBP/receptor site-specific binding. The complete hexasaccharide repeating unit was modelled and found to aptly fit the extended binding site. The specificity observed in in vivo phage adhesion assays could be interpreted in view of the reported structure. Therefore, by combining synthetic carbohydrate chemistry, X-ray crystallography and phage plaquing assays, we suggest that phage adsorption results from distinct recognition of the RBP towards the core TriS or the remaining residues of the hexasacchride receptor. This study provides a novel insight into the adsorption process of phages targeting saccharides as their receptors.
authors.affiliation: Centre for Molecular Innovation and Drug Discovery, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: McCabe
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS, Marseille, UMR, 7257, France.|Aix-Marseille University, Campus de Luminy, Case 932, Marseille, 13288, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Spinelli
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS, Marseille, UMR, 7257, France.|Aix-Marseille University, Campus de Luminy, Case 932, Marseille, 13288, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Farenc
authors.affiliation: Groupe de recherche en écologie buccale & Félix d'Hérelle Reference Center for Bacterial Viruses, Faculté de médecine dentaire, Université Laval, Québec, G1V 0A6, Canada.|Département de biochimie, de microbiologie et de bio-informatique, Faculté des sciences et de génie, Université Laval, Québec, G1V 0A6, Canada.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labbé
authors.affiliation: Groupe de recherche en écologie buccale & Félix d'Hérelle Reference Center for Bacterial Viruses, Faculté de médecine dentaire, Université Laval, Québec, G1V 0A6, Canada.
authors.forename: Denise
authors.initials: D
authors.lastname: Tremblay
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS, Marseille, UMR, 7257, France.|Aix-Marseille University, Campus de Luminy, Case 932, Marseille, 13288, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Blangy
authors.affiliation: Centre for Molecular Innovation and Drug Discovery, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Oscarson
authors.affiliation: Groupe de recherche en écologie buccale & Félix d'Hérelle Reference Center for Bacterial Viruses, Faculté de médecine dentaire, Université Laval, Québec, G1V 0A6, Canada.|Département de biochimie, de microbiologie et de bio-informatique, Faculté des sciences et de génie, Université Laval, Québec, G1V 0A6, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Moineau
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS, Marseille, UMR, 7257, France.|Aix-Marseille University, Campus de Luminy, Case 932, Marseille, 13288, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Cambillau
mesh_terms: D001435:Bacteriophages / Q000378:metabolism*; D001665:Binding Sites; D002236:Carbohydrate Conformation; D018360:Crystallography, X-Ray; D013294:Lactococcus lactis / Q000378:metabolism; D008958:Models, Molecular; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*; D014312:Trisaccharides / Q000138:chemical synthesis
chemical_list: D011135:Polysaccharides, Bacterial; D011991:Receptors, Virus; D014312:Trisaccharides