The <i>Neosartorya fischeri</i> Antifungal Protein 2 (NFAP2): A New Potential Weapon against Multidrug-Resistant <i>Candida auris</i> Biofilms

The <i>Neosartorya fischeri</i> Antifungal Protein 2 (NFAP2): A New Potential Weapon against Multidrug-Resistant <i>Candida auris</i> Biofilms

<i>Candida auris</i> is a potential multidrug-resistant pathogen able to persist on indwelling devices as a biofilm, which serve as a source of catheter-associated infections. <i>Neosartorya fischeri</i> antifungal protein 2 (NFAP2) is a cysteine-rich, cationic protein with p...

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Bibliographic Details
Main Authors: Renátó Kovács, Fruzsina Nagy, Zoltán Tóth, Lajos Forgács, Liliána Tóth, Györgyi Váradi, Gábor K. Tóth, Karina Vadászi, Andrew M. Borman, László Majoros, László Galgóczy
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:International Journal of Molecular Sciences
Subjects:
antifungal lock therapy
<i>Candida auris</i>
biofilm
NFAP2
drug–drug interaction
antifungal susceptibility testing
Online Access:https://www.mdpi.com/1422-0067/22/2/771
Description
Summary:<i>Candida auris</i> is a potential multidrug-resistant pathogen able to persist on indwelling devices as a biofilm, which serve as a source of catheter-associated infections. <i>Neosartorya fischeri</i> antifungal protein 2 (NFAP2) is a cysteine-rich, cationic protein with potent anti-<i>Candida</i> activity. We studied the in vitro activity of NFAP2 alone and in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin against <i>C. auris</i> 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 μM<sup>2</sup>%, 2.16 μM<sup>2</sup>%, 33.31 μM<sup>2</sup>%, 10.72 μM<sup>2</sup>%, and 111.19 μM<sup>2</sup>% 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 <i>C. auris</i> biofilms.
ISSN:1661-6596
1422-0067

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