sodium-nitrite and Candidiasis

Candida albicansis a leading nosocomial pathogen. Today, candidal biofilms are a significant cause of catheter infections, and such infections are becoming increasingly responsible for the failure of medical-implanted devices.C. albicansforms biofilms in which fungal cells are encased in an autoproduced extracellular polysaccharide matrix. Consequently, the enclosed fungi are protected from antimicrobial agents and host cells, providing a unique niche conducive to robust microbial growth and a harbor for recurring infections. Here we demonstrate that a recently developed platform comprised of nanoparticles that release therapeutic levels of nitric oxide (NO-np) inhibits candidal biofilm formation, destroys the extracellular polysaccharide matrices of mature fungal biofilms, and hinders biofilm development on surface biomaterials such as the lumen of catheters. We found NO-np to decrease both the metabolic activity of biofilms and the cell viability ofC. albicansin vitroandin vivo Furthermore, flow cytometric analysis found NO-np to induce apoptosis in biofilm yeast cellsin vitro Moreover, NO-np behave synergistically when used in combination with established antifungal drug therapies. Here we propose NO-np as a novel treatment modality, especially in combination with standard antifungals, for the prevention and/or remediation of fungal biofilms on central venous catheters and other medical devices.

Topics: Animals; Antifungal Agents; Apoptosis; Biofilms; Candida albicans; Candidiasis; Catheter-Related Infections; Catheterization, Central Venous; Chitosan; Disease Models, Animal; Drug Therapy, Combination; Female; Fluconazole; Fungal Polysaccharides; Hyphae; Microbial Sensitivity Tests; Microbial Viability; Nanoparticles; Nitric Oxide; Nitric Oxide Donors; Organosilicon Compounds; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Sodium Nitrite; Voriconazole