|Title||Inhibition and dispersion of Pseudomonas aeruginosa biofilms by glycopeptide dendrimers targeting the fucose-specific lectin LecB.|
|Publication Type||Journal Article|
|Year of Publication||2008|
|Authors||Johansson, E. M. V., S. A. Crusz, E. Kolomiets, L. Buts, R. U. Kadam, M. Cacciarini, K-M. Bartels, S. P. Diggle, M. Cámara, P. Williams, R. Loris, C. Nativi, F. Rosenau, K-E. Jaeger, T. Darbre, and J-L. Reymond|
|Date Published||2008 Dec 22|
|Type of Article||lectins|
|Keywords||Amino Acid Sequence, Bacterial Adhesion, Bacterial Outer Membrane Proteins, Biofilms, Dendrimers, Drug Delivery Systems, Fucose, Glycopeptides, Lectins, Ligands, Models, Molecular, Molecular Structure, Pseudomonas aeruginosa|
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.
|Alternate Journal||Chem. Biol.|
|Grant List||071313/Z/03/Z / / Wellcome Trust / United Kingdom|
Inhibition and dispersion of Pseudomonas aeruginosa biofilms by glycopeptide dendrimers targeting the fucose-specific lectin LecB.