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 |
Journal | Chem Biol |
Volume | 15 |
Issue | 12 |
Pagination | 1249-57 |
Date Published | 2008 Dec 22 |
Type of Article | lectins |
ISSN | 1879-1301 |
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 |
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. |
DOI | 10.1016/j.chembiol.2008.10.009 |
Alternate Journal | Chem. Biol. |
PubMed ID | 19101469 |
Grant List | 071313/Z/03/Z / / Wellcome Trust / United Kingdom |
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