Guimarães Thomas Z A, Mello Érica O, Lucas Douglas R, Damica Filipe Z, Magalhães Fadi S S, Basso Luís G M, Carvalho André O, Gomes Valdirene M, Taveira Gabriel B
Laboratório de Fisiologia e Bioquímica de Microrganismos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro 28013-602, Brazil.
Laboratório de Ciências Físicas, Centro de Ciência e Tecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro 28013-602, Brazil.
ACS Bio Med Chem Au. 2025 May 13;5(4):620-636. doi: 10.1021/acsbiomedchemau.5c00020. eCollection 2025 Aug 20.
The growing threat of fungal infections, driven by increasing drug resistance, has become a major global health concern. Candidiasis, a common human infection, is associated with high mortality, particularly in invasive cases. Among non- (NAC) species, (renamed ) is of clinical importance because of its intrinsic resistance to fluconazole, complicating treatment options. This study evaluated the antifungal efficacy and safety of the bioinspired peptide Def2.1 (CDF-GK) against NAC species, with a specific focus on , through a series of and tests. CDF-GK effectively inhibited the growth of several yeast species, including , , , and , with MIC values ranging from 3.12 to 200 μM. The peptide demonstrated particularly strong activity against , with an MIC of 25 μM, an MFC of 50 μM, and an IC of 5 μM, surpassing the effectiveness of fluconazole. Additionally, CDF-GK inhibited biofilm formation, caused 100% cell death within 1 h, permeabilized the cell membrane, interacted with ergosterol, induced oxidative stress, mitochondrial dysfunction, and vacuolar fragmentation, and entered the intracellular space of . assays using larvae confirmed the low toxicity of CDF-GK, even at high concentrations, and significantly improved the survival of infected larvae with minimal activation of cellular and humoral immune responses. These findings indicate that CDF-GK holds great promise as a therapeutic agent for infections, as it combines potent antifungal action with safety in both and models.
耐药性不断增加导致真菌感染的威胁日益严重，已成为全球主要的健康问题。念珠菌病是一种常见的人类感染，死亡率很高，尤其是在侵袭性病例中。在非白色念珠菌（NAC）物种中，（重新命名为）因其对氟康唑的固有耐药性而具有临床重要性，这使得治疗选择变得复杂。本研究通过一系列体外和体内试验，评估了仿生肽Def2.1（CDF-GK）对NAC物种的抗真菌疗效和安全性，特别关注了。CDF-GK有效地抑制了几种酵母菌种的生长，包括、、和，MIC值范围为3.12至200μM。该肽对表现出特别强的活性，MIC为25μM，MFC为50μM，IC为5μM，超过了氟康唑的有效性。此外，CDF-GK抑制生物膜形成，在1小时内导致100%的细胞死亡，使细胞膜通透性增加，与麦角甾醇相互作用，诱导氧化应激、线粒体功能障碍和液泡破碎，并进入的细胞内空间。使用幼虫进行的体内试验证实即使在高浓度下CDF-GK的毒性也很低，并且在最小程度激活细胞和体液免疫反应的情况下显著提高了感染幼虫的存活率。这些发现表明，CDF-GK作为一种治疗感染的药物具有很大的前景，因为它在体外和体内模型中都兼具强大的抗真菌作用和安全性。
