Enhancing the fungicidal activity of amphotericin B via vacuole disruption by benzyl isothiocyanate, a cruciferous plant constituent,Letters in Applied Microbiology

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Enhancing the fungicidal activity of amphotericin B via vacuole disruption by benzyl isothiocyanate, a cruciferous plant constituent
Letters in Applied Microbiology ( IF 2.0 ) Pub Date : 2020-12-08 , DOI: 10.1111/lam.13425
N. Yamada ₁ , W. Murata _{1,

2} , Y. Yamaguchi ₁ , K.‐I. Fujita ₁ , A. Ogita _{1,

3} , T. Tanaka _{1,

3}

Affiliation

Amphotericin B (AmB), a typical polyene macrolide antifungal agent, is widely used to treat systemic mycoses. In the present study, we show that the fungicidal activity of AmB was enhanced by benzyl isothiocyanate (BITC), a cruciferous plant-derived compound, in the budding yeast, Saccharomyces cerevisiae. In addition to forming a molecular complex with ergosterol present in fungal cell membranes to form K+ -permeable ion channels, AmB has been recognized to mediate vacuolar membrane disruption resulting in lethal effects. BITC showed no effect on AmB-induced plasma membrane permeability; however, it amplified AmB-induced vacuolar membrane disruption in S. cerevisiae. Furthermore, the BITC-enhanced fungicidal effects of AmB significantly decreased cell viability due to the disruption of vacuoles in the pathogenic fungus Candida albicans. The application of the combinatorial antifungal effect of AmB and BITC may aid in dose reduction of AmB in clinical antifungal therapy and consequently decrease side effects in patients. These results also have significant implications for the development of vacuole-targeting chemotherapy against fungal infections.

中文翻译：

通过异硫氰酸苄酯（一种十字花科植物成分）破坏液泡增强两性霉素 B 的杀真菌活性

两性霉素 B (AmB) 是一种典型的多烯大环内酯类抗真菌剂，广泛用于治疗全身性真菌病。在本研究中，我们表明在芽殖酵母酿酒酵母中，异硫氰酸苄酯 (BITC) 增强了 AmB 的杀真菌活性，BITC 是一种十字花科植物衍生化合物。除了与真菌细胞膜中存在的麦角甾醇形成分子复合物以形成 K+ 可渗透的离子通道外，AmB 还被认为可介导液泡膜破裂，从而导致致死效应。BITC 对 AmB 诱导的质膜通透性没有影响；然而，它在酿酒酵母中放大了 AmB 诱导的液泡膜破坏。此外，由于致病真菌白色念珠菌中的液泡被破坏，AmB 的 BITC 增强的杀菌作用显着降低了细胞活力。AmB 和 BITC 联合抗真菌作用的应用可能有助于减少 AmB 在临床抗真菌治疗中的剂量，从而减少患者的副作用。这些结果对于开发针对真菌感染的液泡靶向化疗也具有重要意义。

更新日期：2020-12-08

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