菌物学报2025，Vol.44Issue(8)：116-128,13.DOI:10.13346/j.mycosystema.250035
钙调蛋白激酶转录抑制剂calmidazolium chloride抗烟曲霉及广谱活性研究
The anti-Aspergillus fumigatus and broad-spectrum activities of calmodulin kinase transcription inhibitor calmidazolium chloride
摘要
Abstract
Aspergillus fumigatus,a leading cause of invasive aspergillosis,poses a severe threat to human health.Calmodulin pathway plays a pivotal role in regulating A.fumigatus virulence,making it a critical target for antifungal research.Here,we systematically screened the FDA-approved compound library and identified calmidazolium chloride(CMZ)as a potent inhibitor of A.fumigatus growth.By assessing the effects of CMZ at varying concentrations on hyphal growth,conidial survival and germination,secondary metabolism,and calcium signaling pathway gene expression,the antifungal mechanisms of CMZ against A.fumigatus were comprehensively elucidated.CMZ exhibited robust fungicidal activity,achieving a mortality rate of(98.96±1.47)%against A.fumigatus,and suppressing(85.26±1.51)%of conidial germination and reducing the abundance of the virulence-associated metabolite helvolic acid by 98.02%.Mechanistically,CMZ functioned as a calmodulin kinase transcription inhibitor,disrupting intracellular calcium concentration to exert antifungal effects.Strikingly,CMZ demonstrated synergistic antifungal activity when combined with amphotericin B,significantly enhancing the fungicidal efficacy of the latter.Furthermore,CMZ displayed broad-spectrum antifungal activity,inhibiting Mucor hiemalis,Aspergillus flavus,and Fusarium oxysporum with suppression rates of(24.65±0.90)%,(51.99±0.54)%and(49.98±1.62)%,respectively.Our study highlights CMZ as a potent calmodulin kinase transcription inhibitor with dual antifungal modes-direct suppression of A.fumigatus and synergistic enhancement of amphotericin B,providing a promising candidate compound and a potential combination therapy strategy for combating fungal infections.关键词
烟曲霉/calmidazolium chloride/抗真菌活性/广谱作用/联合用药Key words
Aspergillus fumigatus/calmidazolium chloride/antifungal activity/broad-spectrum action/combination therapy引用本文复制引用
雷雨欣,宋自力,王东,尹文兵..钙调蛋白激酶转录抑制剂calmidazolium chloride抗烟曲霉及广谱活性研究[J].菌物学报,2025,44(8):116-128,13.基金项目
国家自然科学基金(32470046) （32470046）
中国科学院基础研究青年团队项目(YSBR-111)This work was supported by the National Natural Science Foundation of China(32470046)and the Chinese Academy of Sciences Project for Young Scientists in Basic Research(YSBR-111). （YSBR-111）
