title: Inhibition and dispersion of Pseudomonas aeruginosa biofilms by glycopeptide dendrimers targeting the fucose-specific lectin LecB.
abstract: The human pathogenic bacterium Pseudomonas aeruginosa produces a fucose-specific lectin, LecB, implicated in tissue attachment and the formation of biofilms. To investigate if LecB inhibition disrupts these processes, high-affinity ligands were obtained by screening two 15,536-member combinatorial libraries of multivalent fucosyl-peptide dendrimers. The most potent LecB-ligands identified were dendrimers FD2 (C-Fuc-LysProLeu)(4)(LysPheLysIle)(2)LysHisIleNH(2) (IC(50) = 0.14 microM by ELLA) and PA8 (OFuc-LysAlaAsp)(4)(LysSerGlyAla)(2)LysHisIleNH(2) (IC(50) = 0.11 microM by ELLA). Dendrimer FD2 led to complete inhibition of P. aeruginosa biofilm formation (IC(50) approximately 10 microM) and induced complete dispersion of established biofilms in the wild-type strain and in several clinical P. aeruginosa isolates. These experiments suggest that LecB inhibition by high-affinity multivalent ligands could represent a therapeutic approach against P. aeruginosa infections by inhibition of biofilm formation and dispersion of established biofilms.
authors.affiliation: Department of Chemistry and Biochemistry, University of Berne, Freiestrasse 3, CH-3012 Berne, Switzerland.
authors.forename: Emma M V
authors.initials: EM
authors.lastname: Johansson
authors.forename: Shanika A
authors.initials: SA
authors.lastname: Crusz
authors.forename: Elena
authors.initials: E
authors.lastname: Kolomiets
authors.forename: Lieven
authors.initials: L
authors.lastname: Buts
authors.forename: Rameshwar U
authors.initials: RU
authors.lastname: Kadam
authors.forename: Martina
authors.initials: M
authors.lastname: Cacciarini
authors.forename: Kai-Malte
authors.initials: KM
authors.lastname: Bartels
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Diggle
authors.forename: Miguel
authors.initials: M
authors.lastname: Cámara
authors.forename: Paul
authors.initials: P
authors.lastname: Williams
authors.forename: Remy
authors.initials: R
authors.lastname: Loris
authors.forename: Cristina
authors.initials: C
authors.lastname: Nativi
authors.forename: Frank
authors.initials: F
authors.lastname: Rosenau
authors.forename: Karl-Erich
authors.initials: KE
authors.lastname: Jaeger
authors.forename: Tamis
authors.initials: T
authors.lastname: Darbre
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Reymond
mesh_terms: D000595:Amino Acid Sequence; D001422:Bacterial Adhesion / Q000187:drug effects; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects*; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems; D005643:Fucose / Q000737:chemistry / Q000378:metabolism; D006020:Glycopeptides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D037102:Lectins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D050091:Dendrimers; C534598:FD2 dendrimer; D006020:Glycopeptides; C534600:LecB protein, Pseudomonas aeruginosa; D037102:Lectins; D008024:Ligands; C534599:PA8 dendrimer; D005643:Fucose