Author/Authors :
Emma M.V. Johansson، نويسنده , , Shanika A. Crusz، نويسنده , , Elena Kolomiets، نويسنده , , Lieven Buts، نويسنده , , Rameshwar U. Kadam، نويسنده , , Martina Cacciarini، نويسنده , , Kai-Malte Bartels، نويسنده , , Stephen P. Diggle، نويسنده , , Miguel C?mara، نويسنده , , Paul Williams، نويسنده , , Remy Loris، نويسنده , , Cristina Nativi، نويسنده , , Frank Rosenau، نويسنده , , Karl-Erich Jaeger، نويسنده , , Tamis Darbre، نويسنده , , J، نويسنده ,
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 LysHisIleNH2 (IC50 = 0.14 μM by ELLA) and PA8 (OFuc-LysAlaAsp)4(LysSerGlyAla)2 LysHisIleNH2 (IC50 = 0.11 μM by ELLA). Dendrimer FD2 led to complete inhibition of P. aeruginosa biofilm formation (IC50 ∼ 10 μM) 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.
