Antiadhesive properties of glycoclusters against Pseudomonas aeruginosa lung infection.

Abstract

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.

• Authors: Amine M Boukerb, Audric Rousset, Nicolas Galanos, Jean-Baptiste Méar, Marion Thépaut, Teddy Grandjean, Emilie Gillon, Samy Cecioni, Claire Abderrahmen, Karine Faure, David Redelberger, Eric Kipnis, Rodrigue Dessein, Stéphane Havet, Benoit Darblade, Susan E Matthews, Sophie de Bentzmann, Benoit Guéry, Benoit Cournoyer, Anne Imberty, Sébastien Vidal
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 57 Issue 24 Pg. 10275-89 (Dec 26 2014) ISSN: 1520-4804 [Electronic] United States
• PMID: 25419855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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