title: Antiadhesive properties of glycoclusters against Pseudomonas aeruginosa lung infection.
abstract: Pseudomonas aeruginosa lung infections are a major cause of death in cystic fibrosis and hospitalized patients. Treating these infections is becoming difficult due to the emergence of conventional antimicrobial multiresistance. While monosaccharides have proved beneficial against such bacterial lung infection, the design of several multivalent glycosylated macromolecules has been shown to be also beneficial on biofilm dispersion. In this study, calix[4]arene-based glycoclusters functionalized with galactosides or fucosides have been synthesized. The characterization of their inhibitory properties on Pseudomonas aeruginosa aggregation, biofilm formation, adhesion on epithelial cells, and destruction of alveolar tissues were performed. The antiadhesive properties of the designed glycoclusters were demonstrated through several in vitro bioassays. An in vivo mouse model of lung infection provided an almost complete protection against Pseudomonas aeruginosa with the designed glycoclusters.
authors.affiliation: Equipe de Recherche, Bactéries Pathogènes Opportunistes et Environnement, UMR CNRS 5557 Ecologie Microbienne, Université Lyon 1 & VetAgro Sup , 43 Boulevard du 11 Novembre 1918, F-69622 Villeurbanne, France.
authors.forename: Amine M
authors.initials: AM
authors.lastname: Boukerb
authors.forename: Audric
authors.initials: A
authors.lastname: Rousset
authors.forename: Nicolas
authors.initials: N
authors.lastname: Galanos
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Méar
authors.forename: Marion
authors.initials: M
authors.lastname: Thépaut
authors.forename: Teddy
authors.initials: T
authors.lastname: Grandjean
authors.forename: Emilie
authors.initials: E
authors.lastname: Gillon
authors.forename: Samy
authors.initials: S
authors.lastname: Cecioni
authors.forename: Claire
authors.initials: C
authors.lastname: Abderrahmen
authors.forename: Karine
authors.initials: K
authors.lastname: Faure
authors.forename: David
authors.initials: D
authors.lastname: Redelberger
authors.forename: Eric
authors.initials: E
authors.lastname: Kipnis
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Dessein
authors.forename: Stéphane
authors.initials: S
authors.lastname: Havet
authors.forename: Benoit
authors.initials: B
authors.lastname: Darblade
authors.forename: Susan E
authors.initials: SE
authors.lastname: Matthews
authors.forename: Sophie
authors.initials: S
authors.lastname: de Bentzmann
authors.forename: Benoit
authors.initials: B
authors.lastname: Guéry
authors.forename: Benoit
authors.initials: B
authors.lastname: Cournoyer
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.forename: Sébastien
authors.initials: S
authors.lastname: Vidal
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects*; D047250:Calixarenes / Q000737:chemistry*; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006031:Glycosylation; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008956:Models, Chemical; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; C102929:LecA protein, bacteria; C534600:LecB protein, Pseudomonas aeruginosa; D037102:Lectins; D047250:Calixarenes