title: 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.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, NYIT College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, New York, USA.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Ahmadi
authors.affiliation: Department of Biomedical Sciences, NYIT College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, New York, USA.
authors.forename: Hiu Ham
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Howard University College of Medicine, Washington, DC, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Sanchez
authors.affiliation: Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Friedman
authors.affiliation: Department of Urology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Moses T
authors.initials: MT
authors.lastname: Tar
authors.affiliation: Department of Urology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Kelvin P
authors.initials: KP
authors.lastname: Davies
authors.affiliation: Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine, Bronx, New York, USA Departments of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
authors.affiliation: Department of Biomedical Sciences, NYIT College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, New York, USA lmarti13@nyit.edu.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Martinez
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D055499:Catheter-Related Infections / Q000188:drug therapy* / Q000382:microbiology; D002405:Catheterization, Central Venous; D048271:Chitosan / Q000737:chemistry; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D015725:Fluconazole / Q000494:pharmacology; D062610:Fungal Polysaccharides / Q000037:antagonists & inhibitors / Q000737:chemistry; D025301:Hyphae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry; D009569:Nitric Oxide / Q000138:chemical synthesis / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology; D017646:Organosilicon Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012977:Sodium Nitrite / Q000737:chemistry; D065819:Voriconazole / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D062610:Fungal Polysaccharides; D020030:Nitric Oxide Donors; D017646:Organosilicon Compounds; C500739:tetramethyl orthosilicate; D009569:Nitric Oxide; D015725:Fluconazole; D048271:Chitosan; D065819:Voriconazole; D012977:Sodium Nitrite
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