Pseudomonas aeruginosa Biofilm Eradication via Nitric Oxide-Releasing Cyclodextrins

Pseudomonas aeruginosa is the main contributor to the morbidity and mortality of cystic fibrosis (CF) patients. Chronic respiratory infections are rarely eradicated due to protection from CF mucus and the biofilm matrix. The composition of the biofilm matrix determines its viscoelastic properties and affects antibiotic efficacy. Nitric oxide (NO) can both disrupt the physical structure of the biofilm and eradicate interior colonies. The effects of a CF-like growth environment on P. aeruginosa biofilm susceptibility to NO were investigated using parallel plate macrorheology and particle tracking microrheology. Biofilms grown in the presence of mucins and DNA contained greater concentrations of DNA in the matrix and exhibited concomitantly larger viscoelastic moduli compared to those grown in tryptic soy broth. Greater viscoelastic moduli correlated with increased tolerance to tobramycin and colistin. Remarkably, NO-releasing cyclodextrins eradicated all biofilms at the same concentration. The capacity of NO-releasing cyclodextrins to eradicate P. aeruginosa biofilms irrespective of matrix composition suggests that NO-based therapies may be superior antibiofilm treatments compared to conventional antibiotics.