Wang Ying, Wu Xiaoyan, Fan Xiyuan, Han Chanxu, Zheng Fangliang, Zhang Zhenying
Academy of Life Science, Liaoning University, Shenyang, China.
Department of Dermatology, University of Hong Kong Shenzhen Hospital, Shenzhen, China.
Front Microbiol. 2025 Apr 29;16:1546020. doi: 10.3389/fmicb.2025.1546020. eCollection 2025.
Sporotrichosis is a fungal disease caused by a complex of , leading to chronic infections of the epidermis and subcutaneous tissue in both humans and animals.
Through virtual screening targeting the key gene A to screen out the small-molecule drugs to treat Sporotrichosis. To further validate the antifungal activity of small-molecule drugs, growth curves, minimum bactericidal concentration (MBC), and minimum inhibitory concentration (MIC) for () and () were measured. In addition, we have done animal experiments to explore the function of the drugs. At the same time, qRT-PCR and transcriptome were used to verify the important role of A gene in .
Azelastine and Mefloquine effectively inhibit S. globosa and S. schenckii. MBC, and MIC for and confirmed that both Azelastine and Mefloquine inhibited the growth of and . Additionally, animal experiments demonstrated that Azelastine and Mefloquine reduced skin lesions in mice; post-treatment observations revealed improvements in inflammatory infiltration and granuloma formation. Through transcriptome analysis and qRT-PCR for validation, our findings demonstrate that the A gene plays a crucial role in regulating the attachment of the cell wall to the host matrix and in melanin regulation. Notably, when the A gene was inhibited, there was a marked increase in the expression of repair genes. These results emphasize the significance of the A gene in the biology of .
Two small-molecule drugs exhibit the ability to inhibit and treat sporotrichosis both in vitro and in murine models, suggesting their potential for development as therapeutic agents for sporotrichosis. And qRT-PCR and transcriptome results underscore the significance of the A gene in . Our results lay the foundation for the search for new treatments for other mycosis.
孢子丝菌病是一种由复合体引起的真菌病，可导致人和动物的表皮及皮下组织慢性感染。
通过针对关键基因A的虚拟筛选来筛选治疗孢子丝菌病的小分子药物。为进一步验证小分子药物的抗真菌活性，测定了针对（）和（）的生长曲线、最低杀菌浓度（MBC）和最低抑菌浓度（MIC）。此外，我们进行了动物实验以探索药物的功能。同时，使用qRT-PCR和转录组来验证A基因在中的重要作用。
氮卓斯汀和甲氟喹能有效抑制球形孢子丝菌和申克孢子丝菌。针对和的MBC及MIC证实，氮卓斯汀和甲氟喹均能抑制和的生长。此外，动物实验表明氮卓斯汀和甲氟喹可减轻小鼠的皮肤损伤；治疗后的观察显示炎症浸润和肉芽肿形成有所改善。通过转录组分析和qRT-PCR验证，我们的研究结果表明A基因在调节细胞壁与宿主基质的附着以及黑色素调节中起关键作用。值得注意的是，当A基因被抑制时，修复基因的表达显著增加。这些结果强调了A基因在生物学中的重要性。
两种小分子药物在体外和小鼠模型中均表现出抑制和治疗孢子丝菌病的能力，表明它们有开发成为孢子丝菌病治疗药物的潜力。并且qRT-PCR和转录组结果强调了A基因在中的重要性。我们的结果为寻找其他真菌病的新治疗方法奠定了基础。
