Yue Daifan, Zheng Dongming, Yang Linlan, Bai Yuxin, Song Zhen, Li Dongmei, Yu Xiaoqin, Li Yan
College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Department of Nuclear Medicine, Ya'an People's Hospital, Ya'an, 625000, China.
Microb Pathog. 2025 Mar;200:107370. doi: 10.1016/j.micpath.2025.107370. Epub 2025 Feb 8.
Invasive fungal infection is usually caused by Candida albicans infection, which has a high incidence rate and mortality in critically ill patients. New drugs are needed to combat this pathogen since the limited treatment options currently available and increasing resistance to existing drugs. Berberine (BBR) is an active compound in Coptis chinensis, Phellodendron chinense and Radix berberidis, which is clinically used to treat inflammatory bowel disease, but its inhibitory effect on drug-resistant fungi has not been clarified. In this study, based on the evidence of BBR inhibiting the expression of azole-resistance genes, reducing cell adhesion and disrupting biofilm formation, transcriptome analysis revealed that the disruption of iron acquisition pathway may be the core link in BBR inhibiting drug-resistant fungi. Combined with the subsequent experimental results, including the reduction of intracellular ferrous ion content, the weakening of iron reductase activity and the overall downregulation of the coding gene of the high-affinity iron reduction system, it is speculated that the fungal growth defect under BBR treatment is the result of the interruption of the high-affinity iron acquisition pathway. Ftr1 plays a central role in the drug targeting of this transport system. Meanwhile, due to the iron deficiency within the cell, the biological function of mitochondria is impaired, ultimately leading to fungal death. This study not only reflects the application value of BBR in the clinical treatment of fungal infections, but also provides a potential strategy to address the current drug-resistance dilemma.
侵袭性真菌感染通常由白色念珠菌感染引起，在重症患者中发病率和死亡率都很高。由于目前可用的治疗选择有限且对现有药物的耐药性不断增加，因此需要新的药物来对抗这种病原体。黄连素（BBR）是黄连、黄柏和三颗针中的一种活性化合物，临床上用于治疗炎症性肠病，但其对耐药真菌的抑制作用尚未阐明。在本研究中，基于BBR抑制唑类耐药基因表达、减少细胞粘附和破坏生物膜形成的证据，转录组分析表明，铁获取途径的破坏可能是BBR抑制耐药真菌的核心环节。结合随后的实验结果，包括细胞内亚铁离子含量的降低、铁还原酶活性的减弱以及高亲和力铁还原系统编码基因的整体下调，推测BBR处理下真菌生长缺陷是高亲和力铁获取途径中断的结果。Ftr1在该转运系统的药物靶向中起核心作用。同时，由于细胞内缺铁，线粒体的生物学功能受损，最终导致真菌死亡。本研究不仅反映了BBR在真菌感染临床治疗中的应用价值，也为解决当前的耐药困境提供了一种潜在策略。
