Antiadhesive properties of glycoclusters against Pseudomonas aeruginosa lung infection

J Med Chem. 2014 Dec 26;57(24):10275-89. doi: 10.1021/jm500038p. Epub 2014 Dec 8.


Pseudomonas aeruginosa lung infections are a major cause of death in cystic fibrosis and hospitalized patients. Treating these infections is becoming difficult due to the emergence of conventional antimicrobial multiresistance. While monosaccharides have proved beneficial against such bacterial lung infection, the design of several multivalent glycosylated macromolecules has been shown to be also beneficial on biofilm dispersion. In this study, calix[4]arene-based glycoclusters functionalized with galactosides or fucosides have been synthesized. The characterization of their inhibitory properties on Pseudomonas aeruginosa aggregation, biofilm formation, adhesion on epithelial cells, and destruction of alveolar tissues were performed. The antiadhesive properties of the designed glycoclusters were demonstrated through several in vitro bioassays. An in vivo mouse model of lung infection provided an almost complete protection against Pseudomonas aeruginosa with the designed glycoclusters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / chemistry
  • Adhesins, Bacterial / metabolism
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Adhesion / drug effects*
  • Biofilms / drug effects*
  • Calixarenes / chemistry*
  • Cells, Cultured
  • Fluorescent Antibody Technique
  • Glycosylation
  • Humans
  • Lectins / chemistry
  • Lectins / metabolism
  • Lung / drug effects*
  • Lung / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Models, Chemical
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / microbiology


  • Adhesins, Bacterial
  • Anti-Bacterial Agents
  • LecA protein, bacteria
  • LecB protein, Pseudomonas aeruginosa
  • Lectins
  • Calixarenes