Bacterial capsular polysaccharides with antibiofilm activity share common biophysical and electrokinetic properties

Joaquín Bernal-Bayard, Jérôme Thiebaud, Marina Brossaud, Audrey Beaussart, Céline Caillet, Yves Waldvogel, Laetitia Travier, Sylvie Létoffé, Thierry Fontaine, Bachra Rokbi, Philippe Talaga, Christophe Beloin, Noëlle Mistretta (), Jérôme F. L. Duval () and Jean-Marc Ghigo ()
Additional contact information
Joaquín Bernal-Bayard: Institut Pasteur Université Paris Cité, CNRS UMR 6047, Genetics of Biofilms laboratory
Jérôme Thiebaud: Campus Mérieux
Marina Brossaud: Campus Mérieux
Audrey Beaussart: Université de Lorraine, CNRS, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC)
Céline Caillet: Université de Lorraine, CNRS, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC)
Yves Waldvogel: Université de Lorraine, CNRS, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC)
Laetitia Travier: Institut Pasteur Université Paris Cité, CNRS UMR 6047, Genetics of Biofilms laboratory
Sylvie Létoffé: Institut Pasteur Université Paris Cité, CNRS UMR 6047, Genetics of Biofilms laboratory
Thierry Fontaine: Université Paris Cité, INRAE, USC2019, Fungal Biology and Pathogenicity laboratory
Bachra Rokbi: Campus Mérieux
Philippe Talaga: Campus Mérieux
Christophe Beloin: Institut Pasteur Université Paris Cité, CNRS UMR 6047, Genetics of Biofilms laboratory
Noëlle Mistretta: Campus Mérieux
Jérôme F. L. Duval: Université de Lorraine, CNRS, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC)
Jean-Marc Ghigo: Institut Pasteur Université Paris Cité, CNRS UMR 6047, Genetics of Biofilms laboratory

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Bacterial biofilms are surface-attached communities that are difficult to eradicate due to a high tolerance to antimicrobial agents. The use of non-biocidal surface-active compounds to prevent the initial adhesion and aggregation of bacterial pathogens is a promising alternative to antibiotic treatments and several antibiofilm compounds have been identified, including some capsular polysaccharides released by various bacteria. However, the lack of chemical and mechanistic understanding of the activity of these polymers limits their use to control biofilm formation. Here, we screen a collection of 31 purified capsular polysaccharides and first identify seven new compounds with non-biocidal activity against Escherichia coli and/or Staphylococcus aureus biofilms. We measure and theoretically interpret the electrophoretic mobility of a subset of 21 capsular polysaccharides under applied electric field conditions, and we show that active and inactive polysaccharide polymers display distinct electrokinetic properties and that all active macromolecules share high intrinsic viscosity features. Despite the lack of specific molecular motif associated with antibiofilm properties, the use of criteria including high density of electrostatic charges and permeability to fluid flow enables us to identify two additional capsular polysaccharides with broad-spectrum antibiofilm activity. Our study therefore provides insights into key biophysical properties discriminating active from inactive polysaccharides. The characterization of a distinct electrokinetic signature associated with antibiofilm activity opens new perspectives to identify or engineer non-biocidal surface-active macromolecules to control biofilm formation in medical and industrial settings.

Date: 2023
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DOI: 10.1038/s41467-023-37925-8

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