Zhong Jing, Yan Xiayi, Zuo Xin, Zhao Xuan, Yang Jiahui, Dou Qin, Peng Lulu, Zhu Yuxiang, Xiao Yichen, Bian Zeran, He Dalian, Xu Qiushuang, Wright Stephen, Li Yaoyao, Du Liangcheng, Wang Yan, Yuan Jin
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center Sun Yat-sen University Guangzhou China.
College of Marine Life Sciences, and Institute of Evolution & Marine Biodiversity Ocean University of China Qingdao China.
Bioeng Transl Med. 2022 Mar 10;7(3):e10304. doi: 10.1002/btm2.10304. eCollection 2022 Sep.
Fungal pathogens are common causes of superficial clinical infection. Their increasing drug resistance gradually makes existing antifungal drugs ineffective. Heat stable antifungal factor (HSAF) is a novel antifungal natural product with a unique structure. However, the application of HSAF has been hampered by very low yield in the current microbial producers and from extremely poor solubility in water and common solvents. In this study, we developed an effective mode of treatment applying HSAF to superficial fungal infections. The marine-derived YC36 contains the HSAF biosynthetic gene cluster, which we activated by the interspecific signaling molecule indole. An efficient extraction strategy was used to significantly improve the purity to 95.3%. Scanning electron microscopy images revealed that the Type I collagen-based HSAF (Col-HSAF) has a transparent appearance and good physical properties, and the in vitro sustained-release effect of HSAF was maintained for more than 2 weeks. The effective therapeutic concentration of Col-HSAF against superficial fungal infection was explored, and Col-HSAF showed good biocompatibility, lower clinical scores, mild histological changes, and antifungal capabilities in animals with keratitis and cutaneous candidiasis. In conclusion, Col-HSAF is an antifungal reagent with significant clinical value in the treatment of superficial fungal infections.
真菌病原体是浅表临床感染的常见病因。它们不断增加的耐药性逐渐使现有的抗真菌药物失效。热稳定抗真菌因子（HSAF）是一种结构独特的新型抗真菌天然产物。然而，目前微生物生产者中HSAF的产量极低，且在水和常见溶剂中的溶解度极差，这阻碍了HSAF的应用。在本研究中，我们开发了一种将HSAF应用于浅表真菌感染的有效治疗模式。海洋来源的YC36含有HSAF生物合成基因簇，我们通过种间信号分子吲哚激活了该基因簇。采用了一种高效的提取策略，将纯度显著提高到95.3%。扫描电子显微镜图像显示，基于I型胶原蛋白的HSAF（Col-HSAF）外观透明，物理性质良好，HSAF的体外缓释效果维持了2周以上。探讨了Col-HSAF对浅表真菌感染的有效治疗浓度，Col-HSAF在角膜炎和皮肤念珠菌病动物中表现出良好的生物相容性、较低的临床评分、轻微的组织学变化和抗真菌能力。总之，Col-HSAF是一种在治疗浅表真菌感染方面具有重要临床价值的抗真菌试剂。
