Antiadhesive properties of glycoclusters against Pseudomonas aeruginosa lung infection

Boukerb, Amine M., Rousset, Audric, Galanos, Nicolas, Méar, Jean-Baptiste, Thépaut, Marion, Grandjean, Teddy, Gillon, Emilie, Cecioni, Samy, Abderrahmen, Claire, Faure, Karine, Redelberger, David, Kipnis, Eric, Dessein, Rodrigue, Havet, Stéphane, Darblade, Benoit, Matthews, Susan E., de Bentzmann, Sophie, Guéry, Benoit, Cournoyer, Benoit, Imberty, Anne and Vidal, Sébastien (2014) Antiadhesive properties of glycoclusters against Pseudomonas aeruginosa lung infection. Journal of Medicinal Chemistry, 57 (24). pp. 10275-10289. ISSN 0022-2623

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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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Pharmacy
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Depositing User: Pure Connector
Date Deposited: 14 Apr 2015 09:54
Last Modified: 17 Mar 2020 20:41
URI: https://ueaeprints.uea.ac.uk/id/eprint/53103
DOI: 10.1021/jm500038p

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