Issue 1, 2016

Overcoming antibiotic resistance in Pseudomonas aeruginosa biofilms using glycopeptide dendrimers

Abstract

Antibiotic resistance in the opportunistic pathogen Pseudomonas aeruginosa is partly caused by biofilms forming a physical barrier to antibiotic penetration. Here we focused on modifying tetravalent glycopeptide dendrimer ligands of P. aeruginosa lectins LecB or LecA to increase their biofilm inhibition activity. First heteroglycoclusters were investigated displaying one pair each of LecB specific fucosyl groups and LecA specific galactosyl groups and binding simultaneously to both lectins, one of which gave the first fully resolved crystal structure of a peptide dendrimer as LecB complex providing a structural model for dendrimer–lectin interactions (PDB 5D2A). Biofilm inhibition was increased by introducing additional cationic residues in these dendrimers but resulted in bactericidal effects similar to those of non-glycosylated polycationic antimicrobial peptide dendrimers. In a second approach dendrimers displaying four copies of the natural LecB ligand Lewisa were prepared leading to slightly stronger LecB binding and biofilm inhibition. Finally synergistic application of a LecB specific non-bactericidal antibiofilm dendrimer with the antibiotic tobramycin at sub-inhibitory concentrations of both compounds allowed effective biofilm inhibition and dispersal.

Graphical abstract: Overcoming antibiotic resistance in Pseudomonas aeruginosa biofilms using glycopeptide dendrimers

Supplementary files

Article information

Article type
Edge Article
Submitted
24 sept. 2015
Accepted
23 nov. 2015
First published
25 nov. 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2016,7, 166-182

Author version available

Overcoming antibiotic resistance in Pseudomonas aeruginosa biofilms using glycopeptide dendrimers

G. Michaud, R. Visini, M. Bergmann, G. Salerno, R. Bosco, E. Gillon, B. Richichi, C. Nativi, A. Imberty, A. Stocker, T. Darbre and J. Reymond, Chem. Sci., 2016, 7, 166 DOI: 10.1039/C5SC03635F

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements