Interactions of antimicrobial peptides with biofilms of Pseudomonas aeruginosa

The chronicity of Pseudomonas aeruginosa infections in cystic fibrosis (CF) patients is characterized by its overproduction of the exopolysaccharide alginate, in which bacteria are embedded. Alginate contributes to biofilm-related resistance by acting as a diffusion barrier to positively-charged antimicrobial agents including cationic antimicrobial peptides. Our laboratory recently developed a new category of non-amphipathic antimicrobial peptides originally designed to be transmembrane mimetic model peptides. Peptides of this group above a specific hydrophobicity threshold insert spontaneously into membranes and have antibacterial activity at micromolar concentrations. While investigating the molecular basis of biofilm resistance to peptides, we found that the anionic alginate induces conformational changes in hydrophobic antimicrobial peptides typically associated with insertion of such peptides into membrane environments. The overall results indicate that hydrophilic alginate polymers contain a significant hydrophobic compartment, and behave as an 'auxiliary membrane' for bacteria, thus identifying a unique protective role for biofilm matrices.