Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients
Author
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Madariaga Venegas, Francisco
Author
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Fernández Soto, Roberto
Author
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Duarte, Luisa
Author
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Suárez, Nicole
Author
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Delgadillo, Daniela
Author
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Jara Sandoval, José
Author
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Fernández Ramires, Ricardo
Author
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Urzúa Orellana, Blanca
Author
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Molina Berríos, Alfredo Enrique
Admission date
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2018-03-23T14:05:23Z
Available date
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2018-03-23T14:05:23Z
Publication date
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2017-05-11
Cita de ítem
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Plos One Volumen: 12 Número: 5 (2017)
es_ES
Identifier
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10.1371/journal.pone.0176755
Identifier
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https://repositorio.uchile.cl/handle/2250/146970
Abstract
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Candida albicans biofilms play a key role in denture stomatitis, one of the most common oral pathologies in elderly people. Because biofilms are highly resistant to antifungals, new pharmacological strategies are needed. Aspirin and nitric oxide-donor molecules have both shown antibiofilm effects on C. albicans, making them promising candidates for treatment. In this study, we evaluated the antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C. albicans isolates from denture stomatitis patients in vitro. Disk diffusion assays showed that while NO-ASA had no antifungal effect, the drug potentiated fluconazole inhibition zone diameters, increasing the effect of fluconazole by 20-30% (p<0.05). The effect of NO-ASA on the morphogenesis of C. albicans was evaluated using light microscopy after inducing hyphae formation. For all clinical strains assayed, 125 mu M NO-ASA significantly decreased the number of filamentous cells present (p<0.01). Adhesion to abiotic surfaces, a critical event for biofilm formation, was evaluated in 96-well polystyrene plates using crystal violet assay; 125 mu M NO-ASA significantly inhibited adhesion. Biofilms were observed with scanning electron microscopy (SEM) and quantified using XTT reduction assay. NO-ASA decreased biofilm formation (IC50 ranging from 300 mu M to 700 mu M), consistent with SEM findings of altered biofilm microarchitecture. PGE(2) and carboxy-PTIO ( an NO scavenger) both blocked the antibiofilm effects of NO-ASA, suggesting that the efficacy of NO-ASA may be associated with both inhibition of PGE(2) synthesis and release of NO. NO-ASA is a promising novel antibiofilm agent for treating fluconazole-resistant strains of C. albicans.
es_ES
Patrocinador
dc.description.sponsorship
Fondo Nacional de Desarrollo Cientffico y Tecnologico, proyecto FONDECYT
11140227
Vicerrectoria de Investigacion y Desarrollo (VID)
Universidad de Chile
project U-INICIA
2014-82383
project U-redes
URED-2014-007
Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients