Studies on the in vitro mechanism and in vivo therapeutic effect of the antimicrobial peptide ACP5 against Trichophyton mentagrophytes

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides Pub Date : 2024-02-12 DOI:10.1016/j.peptides.2024.171177

Kuiming Zou , Shaojie Zhang , Kedong Yin , Shiming Ren , Mengjun Zhang , Xiatong Li , Lixin Fan , Ruiling Zhang , Ruifang Li

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引用次数: 0

Abstract

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.

查看原文本刊更多论文

研究抗菌肽 ACP5 对脑毛癣菌的体外机制和体内疗效。

脑癣毛癣菌（Trichophyton mentagrophytes）是一种嗜动物皮癣菌，可导致人类和动物皮肤癣菌病。抗菌肽（AMPs）被认为是克服脑毛癣菌耐药性的有效药物。我们的研究结果表明，阳离子抗菌肽（ACP5）不仅比氟康唑具有更强的抗念珠菌活性，而且对 L929 小鼠成纤维细胞的毒性也低于特比萘芬。值得注意的是，其耐药性诱导后的耐药性发展率低于特比萘芬。本研究旨在评估 ACP5 在体外的杀真菌机制及其在体内治疗皮癣菌感染的潜力。1×MIC浓度的ACP5在体外完全抑制了T.mentagrophytes孢子的萌发。ACP5 严重破坏了菌丝形态，导致菌丝破裂。从机理上讲，ACP5 会诱导产生过多的 ROS，破坏细胞膜的完整性并降低线粒体膜电位，从而对 T. mentagrophytes 造成不可逆的损害。此外，在豚鼠皮癣病模型中，1% ACP5 与市售药物 1%特比萘芬的疗效相似，而且通过组织切片观察，证实了 ACP5 能完全根除皮肤上的齿孢子菌。这些结果表明，ACP5 是一种有希望开发出对抗皮癣菌耐药性的新制剂的候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Peptides 医学-生化与分子生物学

CiteScore

6.40

自引率

6.70%

发文量

130

审稿时长

28 days

期刊介绍： Peptides is an international journal presenting original contributions on the biochemistry, physiology and pharmacology of biological active peptides, as well as their functions that relate to gastroenterology, endocrinology, and behavioral effects. Peptides emphasizes all aspects of high profile peptide research in mammals and non-mammalian vertebrates. Special consideration can be given to plants and invertebrates. Submission of articles with clinical relevance is particularly encouraged.