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Int J Mol Sci ; 22(2)2021 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-33466640

RESUMEN

Candida auris is a potential multidrug-resistant pathogen able to persist on indwelling devices as a biofilm, which serve as a source of catheter-associated infections. Neosartorya fischeri antifungal protein 2 (NFAP2) is a cysteine-rich, cationic protein with potent anti-Candida activity. We studied the in vitro activity of NFAP2 alone and in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin against C. auris biofilms. The nature of interactions was assessed utilizing the fractional inhibitory concentration index (FICI), a Bliss independence model, and LIVE/DEAD viability assay. NFAP2 exerted synergy with all tested antifungals with FICIs ranging between 0.312-0.5, 0.155-0.5, 0.037-0.375, 0.064-0.375, and 0.064-0.375 for fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin, respectively. These results were confirmed using a Bliss model, where NFAP2 produced 17.54 µM2%, 2.16 µM2%, 33.31 µM2%, 10.72 µM2%, and 111.19 µM2% cumulative synergy log volume in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin, respectively. In addition, biofilms exposed to echinocandins (32 mg/L) showed significant cell death in the presence of NFAP2 (128 mg/L). Our study shows that NFAP2 displays strong potential as a novel antifungal compound in alternative therapies to combat C. auris biofilms.


Asunto(s)
Antifúngicos/metabolismo , Biopelículas/efectos de los fármacos , Candida/efectos de los fármacos , Proteínas Fúngicas/metabolismo , Neosartorya/metabolismo , Antifúngicos/farmacología , Candida/fisiología , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Sinergismo Farmacológico , Proteínas Fúngicas/farmacología , Humanos
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