Synthetic peptides against Trichophyton mentagrophytes and T. rubrum: Mechanisms of action and efficiency compared to griseofulvin and itraconazole.

Patrícia G Lima, Pedro F N Souza, Cleverson D T Freitas, Leandro P Bezerra, Nilton A S Neto, Ayrles F B Silva, Jose T A Oliveira, Daniele O B Sousa

Life sciences 2021 Jan 15

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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. 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. 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. The synthetic peptides are more efficient than conventional drug to treat infection caused by dermatophytes being potential molecules to develop new drugs. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Patrícia G Lima, Pedro F N Souza, Cleverson D T Freitas, Leandro P Bezerra, Nilton A S Neto, Ayrles F B Silva, Jose T A Oliveira, Daniele O B Sousa. Synthetic peptides against Trichophyton mentagrophytes and T. rubrum: Mechanisms of action and efficiency compared to griseofulvin and itraconazole. Life sciences. 2021 Jan 15;265:118803