Overcoming antibiotic resistance in Pseudomonas aeruginosa biofilms using glycopeptide dendrimers

Michaud, Gaëlle; Visini, Ricardo; Bergmann, Myriam; 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 > Departement of Chemistry and Biochemistry

UniBE Contributor:

Michaud, Gaëlle; Visini, Ricardo; Bergmann, Myriam; 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:

11 Jan 2017 13:37

Publisher DOI:

10.1039/c5sc03635f

BORIS DOI:

10.7892/boris.81113

URI:

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

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