Dinh Hue, Fernandes Kenya E, Erpf Paige E, Clay Evie J M, Tay Aidan P, Nagy Stephanie S, Schaefer Sebastian, Maharjan Ram, Lenardon Megan D, Multari Dylan H, Haynes Paul A, Paulsen Ian T, Santiago Marina J, Connor Mark, Carter Dee, Cain Amy K
School of Natural Sciences, Macquarie University, North Ryde, New South Wales, Australia.
ARC Centre of Excellence in Synthetic Biology, School of Natural Sciences, Macquarie University, North Ryde, New South Wales, Australia.
PLoS Negl Trop Dis. 2025 Jun 5;19(6):e0013081. doi: 10.1371/journal.pntd.0013081. eCollection 2025 Jun.
Fungal infections pose a major threat to human health with increasing incidence of antifungal resistance globally. Despite the need for novel antifungal drugs, few are currently in clinical development. Here we evaluate the antifungal activity of five phytocannabinoids against several clinically relevant fungal pathogens, with a focus on the priority pathogen Cryptococcus neoformans. Our results demonstrate that Cannabidiol (CBD), and particularly Cannabidivarin (CBDV), have broad activity against C. neoformans and other fungal pathogens, including dermatophytes that cause common tinea. We found that both CBD and CBDV acted in a fungicidal manner and prevented biofilm formation in C. neoformans. Phytocannabinoid treatment impeded factors important for virulence and antifungal resistance, including reduced capsule size and disruption of mature biofilms. Proteomics analysis revealed that the antifungal activity of CBD and CBDV was linked to destabilisation of the membrane, alterations in ergosterol biosynthesis, disruption of metabolic pathways, as well as selective involvement of mitochondrial-associated proteins. We next tested the ability of CBD to topically clear a C. neoformans fungal infection in vivo using the Galleria mellonella burn wound model, and we observed greatly improved survival in the CBD treated larvae. This study illustrates the potential of phytocannabinoids as antifungal treatments and opens up new routes towards development of novel antifungal drugs.
随着全球抗真菌耐药性发病率的增加，真菌感染对人类健康构成了重大威胁。尽管需要新型抗真菌药物，但目前处于临床开发阶段的药物很少。在此，我们评估了五种植物大麻素对几种临床相关真菌病原体的抗真菌活性，重点关注优先病原体新型隐球菌。我们的结果表明，大麻二酚（CBD），尤其是大麻二萜酚（CBDV），对新型隐球菌和其他真菌病原体具有广泛的活性，包括引起常见癣的皮肤癣菌。我们发现CBD和CBDV均以杀菌方式起作用，并防止新型隐球菌形成生物膜。植物大麻素处理阻碍了对毒力和抗真菌耐药性重要的因素，包括减小荚膜大小和破坏成熟生物膜。蛋白质组学分析表明，CBD和CBDV的抗真菌活性与膜的不稳定、麦角固醇生物合成的改变、代谢途径的破坏以及线粒体相关蛋白的选择性参与有关。接下来，我们使用大蜡螟烧伤伤口模型测试了CBD在体内局部清除新型隐球菌真菌感染的能力，我们观察到经CBD处理的幼虫存活率大大提高。这项研究说明了植物大麻素作为抗真菌治疗的潜力，并为开发新型抗真菌药物开辟了新途径。
