Aims

According to the WHO, 20–25% of people worldwide are affected by skin infections caused by dermatophytes, such as those of the Trichophyton genus. Additionally, several dermatophytes have developed resistance to drugs such as griseofulvin and itraconazole. This study tested 2S albumins-derived antimicrobial peptides (AMPs) as alternative antidermatophytic molecules.

Main methods

Membrane pore formation assays, tests to detect overproduction of ROS, scanning electron microscopy (SEM) and fluorescence microscopy (FM) were carried out to provide insight into the mechanisms of antidermatophytic action.

Key findings

All AMPs (at 50 μg mL⁻¹) tested reduced the mycelial growth of T. mentagrophytes and T. rubrum by up to 95%. In contrast, using a concentration 20-fold higher, griseofulvin only inhibited T. mentagrophytes by 35%, while itraconazole was not active against both dermatophytes. Scanning electron and fluorescence microscopies revealed that the six AMPs caused severe damage to hyphal morphology by inducing cell wall rupture, hyphal content leakage, and death. Peptides also induced membrane pore formation and oxidative stress by overproduction of ROS. Based on the stronger activity of peptides than the commercial drugs and the mechanism of action, all six peptides have the potential to be either employed as models to develop new antidermatophytic drugs or as adjuvants to existing ones.

Significance

The synthetic peptides are more efficient than conventional drug to treat infection caused by dermatophytes being potential molecules to develop new drugs.

中文翻译：

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对合成肽须癣毛癣菌和红色毛癣菌：行动与效率的机制相比，灰黄霉素和伊曲康唑

目的

根据世界卫生组织的数据，全世界有20％到25％的人受到皮肤癣菌引起的皮肤感染的影响，例如毛癣菌属。另外，几种皮肤真菌已对诸如灰黄霉素和伊曲康唑的药物产生抗性。这项研究测试了2S白蛋白衍生的抗菌肽（AMPs）作为替代的抗皮肤赘生物分子。

主要方法

进行了膜孔形成分析，检测ROS过量产生的测试，扫描电子显微镜（SEM）和荧光显微镜（FM），以深入了解抗皮肤癣菌作用的机理。

主要发现

所有AMPS（在50微克毫升^-1）测试的减少的菌丝生长须发癣菌和红色毛癣菌由高达95％。相比之下，使用浓度高20倍的灰黄霉素只能抑制薄荷茶减少了35％，而伊曲康唑对两种皮肤真菌均无效。扫描电子显微镜和荧光显微镜检查显示，这六个AMP通过诱导细胞壁破裂，菌丝含量泄漏和死亡而严重损害菌丝形态。肽还通过过量产生ROS诱导膜孔形成和氧化应激。基于肽类比市售药物更强的活性和作用机理，所有六种肽都有潜力被用作开发新的抗皮肤真菌药物的模型或作为现有药物的佐剂。

意义

合成肽比常规药物更有效地治疗由皮肤癣菌引起的感染，而皮肤癣菌是开发新药的潜在分子。