Multivalency effects in Pseudomonas aeruginosa biofilm inhibition and dispersal by glycopeptide dendrimers targeting lectin LecA

Bergmann, Myriam; Michaud, Gaëlle; Visini, Ricardo; Jin, Xian; Gillon, Emilie; Stocker, Achim; Imberty, Anne; Darbre, Tamis; Reymond, Jean-Louis (2015). Multivalency effects in Pseudomonas aeruginosa biofilm inhibition and dispersal by glycopeptide dendrimers targeting lectin LecA. Organic & biomolecular chemistry, 14(1), pp. 138-148. Royal Society of Chemistry 10.1039/C5OB01682G

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The galactose specific lectin LecA partly mediates the formation of antibiotic resistant biofilms by Pseudomonas aeruginosa, an opportunistic pathogen causing lethal airways infections in immunocompromised and cystic fibrosis patients, suggesting that preventing LecA binding to natural saccharides might provide new opportunities for treatment. Here 8-fold (G3) and 16-fold (G4) galactosylated analogs of GalAG2, a tetravalent G2 glycopeptide dendrimer LecA ligand and P. aeruginosa biofilm inhibitor, were obtained by convergent chloroacetyl thioether (ClAc) ligation between 4-fold or 8-fold chloroacetylated dendrimer cores and digalactosylated dendritic arms. Hemagglutination inhibition, isothermal titration calorimetry and biofilm inhibition assays showed that G3 dendrimers bind LecA slightly better than their parent G2 dendrimers and induce complete biofilm inhibition and dispersal of P. aeruginosa biofilms, while G4 dendrimers show reduced binding and no biofilm inhibition. A binding model accounting for the observed saturation of glycopeptide dendrimer galactosyl groups and LecA binding sites is proposed based on the crystal structure of a G3 dendrimer LecA complex.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Bergmann, Myriam; Michaud, Gaëlle; Visini, Ricardo; Jin, Xian; Stocker, Achim; Darbre, Tamis and Reymond, Jean-Louis

Subjects:

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

ISSN:

1477-0520

Publisher:

Royal Society of Chemistry

Language:

English

Submitter:

Achim Stocker

Date Deposited:

09 Nov 2015 11:16

Last Modified:

26 Jun 2016 02:08

Publisher DOI:

10.1039/C5OB01682G

PubMed ID:

26416170

BORIS DOI:

10.7892/boris.72548

URI:

https://boris.unibe.ch/id/eprint/72548

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