Antibiofilm efficacy of nitric oxide-releasing alginates against cystic fibrosis bacterial pathogens.
ACS Infect Dis. 2019 May 28;:
Authors: Ahonen MJR, Dorrier JM, Schoenfisch MH
Colonization of the lungs by biofilm-forming pathogens is a major cause of mortality in cystic fibrosis (CF). In CF patients, these pathogens are difficult to treat due to the additional protection provided by both the biofilm exopolysaccharide matrix and thick, viscous mucus. The antibiofilm efficacy of nitric oxide (NO)-releasing alginates were evaluated against Pseudomonas aeruginosa, Burkholderia cepacia, Staphylococcus aureus, and methicillin-resistant S. aureus biofilms in both aerobic and anaerobic environments. Varying the amine precursor grafted onto alginate oligosaccharides imparted tunable NO storage (~0.1-0.3 µmol/mg) and release kinetics (~4-40 min half-lives) in the artificial sputum media used for biofilm testing. The NO-releasing alginates were highly antibacterial against the four CF-relevant pathogens, achieving a 5-log reduction in biofilm viability after 24-h treatment, with biocidal efficacy dependent on NO-release kinetics. Aerobic biofilms required greater starting NO doses to achieve killing relative to the anaerobic biofilms. Relative to tobramycin (MBEC24h ≥2000 µg/mL) and vancomycin (MBEC24h ≥1000 µg/mL), the NO-releasing alginates proved to be more effective (NO dose ≤520 µg/mL) regardless of growth conditions.
PMID: 31136714 [PubMed – as supplied by publisher]