可用的有效药剂的数量有限,需要开发新的抗真菌剂。我们报告说,一种从calionnicum中分离出的jerveratum型甾体生物碱,具有抗真菌活性。细胞壁突变体的表型比较,K1杀手毒素药敏试验,和细胞壁成分的定量表明,叶尔文显着抑制了β-1,6-葡聚糖的生物合成。温度敏感突变体在参与β-1,6-葡聚糖生物合成的必需基因中存在缺陷,包括BIG1,KEG1,KRE5,KRE9和ROT1,对肉豆蔻过敏。相比之下,KRE6或其同系物SKN1的点突变产生了杰文抗性,说明Jervine的目标是Kre6和Skn1.Jervine具有广谱抗真菌活性,对人类病原真菌有效,包括近平滑念珠菌和克鲁斯念珠菌。它对植物病原真菌也有效,包括灰葡萄孢菌和核菌。Jervine与氟康唑具有协同作用。因此,Jervine,一种用于医药产品的jerveratum型甾体生物碱,代表一类新的抗真菌药,对真菌病和植物病原真菌具有活性。重要性非白色念珠菌念珠菌(NCAC)作为真菌病的原因正在增加。许多抗真菌药物对NCAC的效果较差,限制可用的治疗剂。这里,我们报告说,一种耶氏型甾体生物碱,对NCAC和植物病原真菌有效。Jervine作用于参与β-1,6-葡聚糖生物合成的Kre6和Skn1。已经对Jerveratum型甾体生物碱的骨架进行了充分的研究,最近,它们的抗癌特性已被研究。因此,Jerveratum型生物碱可能用作真菌感染和癌症的治疗方法。
The limited number of available effective agents necessitates the development of new antifungals. We report that
jervine, a jerveratrum-type steroidal alkaloid isolated from Veratrum californicum, has antifungal activity. Phenotypic comparisons of cell wall mutants, K1 killer toxin susceptibility testing, and quantification of cell wall components revealed that β-1,6-glucan biosynthesis was significantly inhibited by jervine. Temperature-sensitive mutants defective in essential genes involved in β-1,6-glucan biosynthesis, including BIG1, KEG1, KRE5, KRE9, and ROT1, were hypersensitive to jervine. In contrast, point mutations in KRE6 or its paralog SKN1 produced
jervine resistance, suggesting that
jervine targets Kre6 and Skn1. Jervine exhibited broad-spectrum antifungal activity and was effective against human-pathogenic fungi, including Candida parapsilosis and Candida krusei. It was also effective against phytopathogenic fungi, including Botrytis cinerea and Puccinia recondita.
Jervine exerted a synergistic effect with fluconazole. Therefore, jervine, a jerveratrum-type steroidal alkaloid used in pharmaceutical products, represents a new class of antifungals active against mycoses and plant-pathogenic fungi. IMPORTANCE Non-Candida albicans Candida species (NCAC) are on the rise as a cause of mycosis. Many antifungal drugs are less effective against NCAC, limiting the available therapeutic agents. Here, we report that jervine, a jerveratrum-type steroidal alkaloid, is effective against NCAC and phytopathogenic fungi.
Jervine acts on Kre6 and Skn1, which are involved in β-1,6-glucan biosynthesis. The skeleton of jerveratrum-type steroidal alkaloids has been well studied, and more recently, their anticancer properties have been investigated. Therefore, jerveratrum-type alkaloids could potentially be applied as treatments for fungal infections and cancer.