Inhibition and dispersion of Pseudomonas aeruginosa biofilms by glycopeptide dendrimers targeting the fucose-specific lectin LecB

Chem Biol. 2008 Dec 22;15(12):1249-57. doi: 10.1016/j.chembiol.2008.10.009.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Adhesion / drug effects
  • Bacterial Outer Membrane Proteins / metabolism
  • Biofilms / drug effects*
  • Dendrimers / chemistry*
  • Dendrimers / pharmacology
  • Drug Delivery Systems*
  • Fucose* / chemistry
  • Fucose* / metabolism
  • Glycopeptides / chemistry*
  • Glycopeptides / genetics
  • Glycopeptides / pharmacology
  • Lectins / chemistry
  • Lectins / genetics
  • Lectins / metabolism*
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / metabolism


  • Bacterial Outer Membrane Proteins
  • Dendrimers
  • FD2 dendrimer
  • Glycopeptides
  • LecB protein, Pseudomonas aeruginosa
  • Lectins
  • Ligands
  • PA8 dendrimer
  • Fucose

Associated data

  • PDB/3DCQ