Nanoparticles shown to inhibit candidal biofilm formation

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Abstract:

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.

Reference:

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. [Epub ahead of print].

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