Regulation of oxidative stress enzymes in Candida auris by Dermaseptin: potential implications for antifungal drug discovery

IF 3.9 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY RSC Advances Pub Date : 2024-11-20 DOI:10.1039/D4RA06392A
Mohmmad Younus Wani, Vartika Srivastava, Tamer S. Saleh, Abdullah Saad Al-Bogami, Faisal Mohammed Aqlan and Aijaz Ahmad
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Abstract

The emergence of Candida auris poses a significant global health threat due to its high mortality rates and multidrug resistance. The development of new antifungal drugs is essential to effectively combat this pathogen. Antimicrobial peptides, such as Dermaseptin, have demonstrated potent anti-Candida activity. This study aimed to investigate the antifungal activity of Dermaseptin against C. auris isolates and its ability to induce oxidative stress and apoptosis. The results revealed the robust anti-Candida activity of Dermaseptin, with a minimum inhibitory concentration (MIC) of 15.62 μg mL−1 and a minimum fungicidal concentration (MFC) of 31.25 μg mL−1. Spectrophotometric analysis demonstrated that Dermaseptin induced significant oxidative stress, as evidenced by the notable differences in the activity of primary antioxidant enzymes and lipid peroxidation (LPO) levels between the treated and untreated control groups. Moreover, Dermaseptin influenced the gene expression of antioxidant enzymes, as confirmed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Additionally, Dermaseptin induced apoptosis in C. auris in a dose-dependent manner. This study highlights the potential of Dermaseptin to inhibit and potentially eradicate C. auris by increasing oxidative stress levels. The low MICs and fungicidal properties of Dermaseptin against C. auris isolates suggest its potential as a candidate for the development of a novel antifungal agent.

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Dermaseptin 对白色念珠菌氧化应激酶的调控:对抗真菌药物发现的潜在影响
由于高死亡率和多重耐药性,念珠菌病的出现对全球健康构成了重大威胁。开发新型抗真菌药物对于有效防治这种病原体至关重要。抗菌肽(如 Dermaseptin)已被证明具有强大的抗念珠菌活性。本研究旨在探讨 Dermaseptin 对白色念珠菌分离株的抗真菌活性及其诱导氧化应激和细胞凋亡的能力。结果显示,Dermaseptin 具有很强的抗念珠菌活性,其最低抑菌浓度(MIC)为 15.62 μg mL-1,最低杀菌浓度(MFC)为 31.25 μg mL-1。分光光度法分析表明,Dermaseptin 会诱发显著的氧化应激,这体现在处理组和未处理对照组之间初级抗氧化酶活性和脂质过氧化物(LPO)水平的显著差异上。此外,经逆转录定量聚合酶链反应(RT-qPCR)证实,Dermaseptin 会影响抗氧化酶的基因表达。此外,Dermaseptin 还能以剂量依赖的方式诱导蛔虫凋亡。这项研究强调了 Dermaseptin 通过增加氧化应激水平来抑制并可能根除真菌的潜力。Dermaseptin对C. auris分离物的低MICs和杀真菌特性表明它有可能成为新型抗真菌药的候选药物。
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来源期刊
RSC Advances
RSC Advances chemical sciences-
CiteScore
7.50
自引率
2.60%
发文量
3116
审稿时长
1.6 months
期刊介绍: An international, peer-reviewed journal covering all of the chemical sciences, including multidisciplinary and emerging areas. RSC Advances is a gold open access journal allowing researchers free access to research articles, and offering an affordable open access publishing option for authors around the world.
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