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

Abstract

AbstractBacterial 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 high-molecular-weight polymers limits their use for control of biofilm formation. Here, we screened a collection of 32 purified capsular polysaccharides and identified seven new compounds with non-biocidal activity against biofilms formed by Escherichia coli and/or Staphylococcus aureus. We analyzed the polysaccharide mobility under applied electric field conditions and showed that active and inactive polysaccharide polymers display distinct electrokinetic properties and that all active macromolecules shared high intrinsic viscosity features. Based on these characteristics, we identified two additional antibiofilm capsular polysaccharides with high density of electrostatic charges and their permeability to fluid flow. Our study therefore provides insights into key biophysical properties discriminating active from inactive polysaccharides. This characterization of a specific electrokinetic signature for polysaccharides displaying antibiofilm activity opens new perspectives to identify or engineer non-biocidal surface-active macromolecules to control biofilm formation in medical and industrial settings.Significance statementSome bacteria produce non-biocidal capsular polysaccharides that reduce the adhesion of bacterial pathogens to surfaces. Due to a lack of molecular and structural definition, the basis of their antiadhesion activity is unknown, thus hindering their prophylactic use for biofilm control. Here, we identified nine new active compounds and compared their composition, structure and biophysical properties with other inactive capsular polysaccharides. Despite the absence of specific molecular motif, we demonstrate that all active polysaccharides share common electrokinetic properties that distinguish them from inactive polymers. This characterization of the biophysical properties of antibiofilm bacterial polysaccharide provides key insights to engineer non-biocidal and bio-inspired surface-active compounds to control bacterial adhesion in medical and industrial settings.