Biofilm Dispersal, Reduced Viscoelasticity, and Antibiotic Sensitization via Nitric Oxide-Releasing Biopolymers

Compared to planktonic bacteria, biofilms are notoriouslydifficultto eradicate due to their inherent protection against the immune responseand antimicrobial agents. Inducing biofilm dispersal to improve susceptibilityto antibiotics is an attractive therapeutic avenue for eradicatingbiofilms. Nitric oxide (NO), an endogenous antibacterial agent, haspreviously been shown to induce biofilm dispersal, but with limitedunderstanding of the effects of NO-release properties. Herein, theantibiofilm effects of five promising NO-releasing biopolymer candidateswere studied by assessing dispersal, changes in biofilm viscoelasticity,and increased sensitization to tobramycin after treatment with NO.A threshold level of NO was needed to achieve biofilm dispersal, withlonger-releasing systems requiring lower concentrations. The mostpositively charged NO-release systems (from the presence of primaryamines) led to the greatest reduction in viscoelasticity of Pseudomonas aeruginosa biofilms. Co-treatment oftobramycin with the NO-releasing biopolymer greatly decreased thedose of tobramycin required to eradicate tobramycin-susceptible and-resistant biofilms in both cellular and tissue models.