Key Laboratory of Functional Molecules for Biomedical Research, Zhengzhou, Henan University of Technology, 450001 Zhengzhou, Henan, PR China; College of Biological Engineering, Henan University of Technology, 450001 Zhengzhou, Henan, PR China.
Key Laboratory of Functional Molecules for Biomedical Research, Zhengzhou, Henan University of Technology, 450001 Zhengzhou, Henan, PR China; College of Information Science and Engineering, Henan University of Technology, 450001 Zhengzhou, Henan, PR China.
Peptides. 2024 May;175:171177. doi: 10.1016/j.peptides.2024.171177. Epub 2024 Feb 12.
Trichophyton mentagrophytes is a zoophilic dermatophyte that can cause dermatophytosis in humans and animals. Antimicrobial peptides (AMPs) are considered as a promising agent to overcome the drug-resistance of T. mentagrophytes. Our findings suggest that cationic antimicrobial peptide (ACP5) not only possesses stronger activity against T. mentagrophytes than fluconazole, but also shows lower toxicity to L929 mouse fibroblast cells than terbinafine. Notably, its resistance development rate after resistance induction was lower than terbinafine. The present study aimed to evaluate the fungicidal mechanism of ACP5 in vitro and its potential to treat dermatophyte infections in vivo. ACP5 at 1 ×MIC completely inhibited T. mentagrophytes spore germination in vitro. ACP5 severely disrupts the mycelial morphology, leading to mycelial rupture. Mechanistically, ACP5 induces excessive ROS production, damaging the integrity of the cell membrane and decreasing the mitochondrial membrane potential, causing irreversible damage in T. mentagrophytes. Furthermore, 1% ACP5 showed similar efficacy to the commercially available drug 1% terbinafine in a guinea pig dermatophytosis model, and the complete eradication of T. mentagrophytes from the skin by ACP5 was verified by tissue section observation. These results indicate that ACP5 is a promising candidate for the development of new agent to combat dermatophyte resistance.
须毛癣菌是一种亲动物性的皮肤癣菌，可引起人类和动物的皮肤癣病。抗菌肽（AMPs）被认为是克服须毛癣菌耐药性的有前途的药物。我们的研究结果表明，阳离子抗菌肽（ACP5）不仅对须毛癣菌的活性比氟康唑强，而且对 L929 小鼠成纤维细胞的毒性比特比萘芬低。值得注意的是，其耐药诱导后耐药发展速度低于特比萘芬。本研究旨在评估 ACP5 体外的杀菌机制及其在体内治疗皮肤癣菌感染的潜力。在体外，1×MIC 的 ACP5 完全抑制须毛癣菌孢子萌发。ACP5 严重破坏菌丝形态，导致菌丝破裂。在机制上，ACP5 诱导过量的 ROS 产生，破坏细胞膜的完整性，降低线粒体膜电位，导致须毛癣菌不可逆转的损伤。此外，1%的 ACP5 在豚鼠皮肤癣病模型中显示出与市售药物 1%特比萘芬相似的疗效，通过组织切片观察证实 ACP5 可从皮肤中完全清除须毛癣菌。这些结果表明，ACP5 是开发新药物对抗皮肤癣菌耐药性的有前途的候选药物。
