Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
Faculty of Pharmacy, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
Int J Mol Sci. 2021 Jan 14;22(2):771. doi: 10.3390/ijms22020771.
is a potential multidrug-resistant pathogen able to persist on indwelling devices as a biofilm, which serve as a source of catheter-associated infections. antifungal protein 2 (NFAP2) is a cysteine-rich, cationic protein with potent anti- activity. We studied the in vitro activity of NFAP2 alone and in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin against 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%, 2.16 μM%, 33.31 μM%, 10.72 μM%, and 111.19 μM% 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 biofilms.
是一种潜在的多药耐药病原体，能够作为生物膜在留置装置上持续存在，作为导管相关性感染的源头。抗菌蛋白 2（NFAP2）是一种富含半胱氨酸的阳离子蛋白，具有强大的抗真菌活性。我们研究了 NFAP2 单独以及与氟康唑、两性霉素 B、阿尼芬净、卡泊芬净和米卡芬净联合应用对生物膜的体外活性。利用部分抑菌浓度指数（FICI）、 Bliss 独立性模型和 LIVE/DEAD 活力测定评估相互作用的性质。NFAP2 与所有测试的抗真菌药物均表现出协同作用，氟康唑、两性霉素 B、阿尼芬净、卡泊芬净和米卡芬净的 FICI 分别为 0.312-0.5、0.155-0.5、0.037-0.375、0.064-0.375 和 0.064-0.375。这些结果通过 Bliss 模型得到了证实，NFAP2 与氟康唑、两性霉素 B、阿尼芬净、卡泊芬净和米卡芬净联合应用时，分别产生了 17.54 μM%、2.16 μM%、33.31 μM%、10.72 μM%和 111.19 μM%的累积协同对数体积。此外，暴露于棘白菌素（32 mg/L）的生物膜在 NFAP2（128 mg/L）存在时显示出明显的细胞死亡。我们的研究表明，NFAP2 作为一种新型抗真菌化合物，具有在替代疗法中对抗生物膜的巨大潜力。
