Candida albicans is 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. albicans form biofilms in which fungal cells are encased in an auto-produced 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 reoccurring 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 of C. albicans in vitro and in vivo. Furthermore, flow cytometric analysis found NO-np to induce apoptosis in biofilm yeast cells in vitro. Moreover, NO-np behaves 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.
Ahmadi, M., Lee, H.H., Sanchez, D.A., Friedman, A.J., Tar, M.T., Davis, K.P., Nosanchuk, J.D. and Martinez, L.R. (2016) Sustained nitric oxide releasing nanoparticles induce cell death in Candida albicans yeast and hyphal cells preventing biofilm formation in vitro and in a rodent central venous catheter model. Antimicrobial Agents and Chemotherapy. January 25th. .
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