期刊
ACS INFECTIOUS DISEASES
卷 5, 期 8, 页码 1327-1335出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.9b00016
关键词
nitric oxide; alginates; antibiofilm; cystic fibrosis
资金
- National Institutes of Health [AI112029]
- Cystic Fibrosis Foundation [Schoen18G0]
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 was 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 (similar to 0.1-0.3 mu mol/mg) and release kinetics (similar to 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 of 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 (the minimum concentration of antibacterial agent required to achieve a 5-log reduction in viability after 24 h, MBEC24h, of >= 2000 mu g/mL) and vancomycin (MBEC24h >= 1000 mu g/mL), the NO-releasing alginates proved to be more effective (NO dose <= 520 mu g/mL) regardless of growth conditions.
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