Abstract：
Candida albicans is the most leading cause of life-threatening fungal invasive infections, especially for vulvovaginal candidiasis (VVC). Resistance and tolerance to common fungicide has risen great demands on alternative strategies for treating C. albicans infections. In the present study, ferroptosis has been proven to occur in C. albicans by directly exposed to FeSO4 via induing hallmarks of ferroptosis, including Fe2+ overload burden, ROS eruption and lipid peroxidation. Transcriptomic profile gave the great hints of the possible mechanism for fungal ferroptosis that FeSO4 disturb pathways associated to ribosome, tyrosine metabolism, triglyceride metabolism and thiamine metabolism, thus mobilizing death-related gene synthesis. Inspired by the results, a FeSO4-loaded hydrogel was prepared as an antifungal agent to treat C. albicans infection. This hydrogel exhibited excellent dressing properties and maintained superior antifungal activity by characterization tests. Besides, mice treated by this composite hydrogel displayed excellent therapeutic efficacy. These results highlighted the potential therapeutic use of FeSO4 as an innovative strategy in treating C. albicans infections by targeting ferroptosis.
摘要：
白色念珠菌是威胁生命的真菌侵袭性感染的最主要原因，尤其是外阴阴道念珠菌病（VVC）。对常见杀真菌剂的抗性和耐受性对治疗白色念珠菌感染的替代策略提出了巨大的要求。在本研究中,已经证明，通过直接暴露于FeSO4，通过插入铁性凋亡的标志，在白色念珠菌中发生铁性凋亡，包括Fe2+过载负荷，ROS爆发和脂质过氧化。转录组谱为真菌铁死亡的可能机制提供了很好的提示，即FeSO4干扰与核糖体相关的途径，酪氨酸代谢，甘油三酯代谢和硫胺素代谢，从而动员与死亡相关的基因合成。受到结果的启发，制备负载FeSO4的水凝胶作为抗真菌剂以治疗白色念珠菌感染。通过表征测试,该水凝胶表现出优异的敷料性质并保持优异的抗真菌活性。此外,用这种复合水凝胶处理的小鼠表现出优异的治疗效果。这些结果强调了FeSO4作为通过靶向铁性凋亡治疗白色念珠菌感染的创新策略的潜在治疗用途。
