Overcoming antibiotic resistance in Pseudomonas aeruginosa biofilms using glycopeptide dendrimers

Michaud, Gaëlle; Visini, Ricardo; Bergman, Manfred Max; Salerno, Gianluca; Bosco, Rosa; Gillon, Emilie; Richichi, Barbara; Nativi, Cristina; Imberty, Anne; Stocker, Achim; Darbre, Tamis; Reymond, Jean-Louis (2016). Overcoming antibiotic resistance in Pseudomonas aeruginosa biofilms using glycopeptide dendrimers. Chemical Science, 7(1), pp. 166-182. The Royal Society of Chemistry 10.1039/c5sc03635f

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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 nonbactericidal
antibiofilm dendrimer with the antibiotic tobramycin at sub-inhibitory concentrations of both
compounds allowed effective biofilm inhibition and dispersal.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Michaud, Gaëlle; Visini, Ricardo; Bergman, Manfred Max; Stocker, Achim; Darbre, Tamis and Reymond, Jean-Louis

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

2041-6520

Publisher:

The Royal Society of Chemistry

Language:

English

Submitter:

Achim Stocker

Date Deposited:

11 Jan 2017 13:37

Last Modified:

24 Feb 2021 01:12

Publisher DOI:

10.1039/c5sc03635f

BORIS DOI:

10.7892/boris.81113

URI:

https://boris.unibe.ch/id/eprint/81113

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