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合成肽的抗真菌潜力:作用机制研究表明合成肽可诱导膜孔形成、DNA降解和细胞凋亡。

Antifungal Potential of Synthetic Peptides against : Mechanism of Action Studies Reveal Synthetic Peptides Induce Membrane-Pore Formation, DNA Degradation, and Apoptosis.

作者信息

Aguiar Tawanny K B, Neto Nilton A S, Freitas Cleverson D T, Silva Ayrles F B, Bezerra Leandro P, Malveira Ellen A, Branco Levi A C, Mesquita Felipe P, Goldman Gustavo H, Alencar Luciana M R, Oliveira Jose T A, Santos-Oliveira Ralph, Souza Pedro F N

机构信息

Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza 60451-970, CE, Brazil.

Department of Fisheries Engineering, Federal University of Ceará, Fortaleza 60455-970, CE, Brazil.

出版信息

Pharmaceutics. 2022 Aug 12;14(8):1678. doi: 10.3390/pharmaceutics14081678.

Abstract

is a human-pathogenic yeast responsible for pneumonia and meningitis, mainly in patients immunocompromised. Infections caused by are a global health concern. Synthetic antimicrobial peptides (SAMPs) have emerged as alternative molecules to cope with fungal infections, including . Here, eight SAMPs were tested regarding their antifungal potential against and had their mechanisms of action elucidated by fluorescence and scanning electron microscopies. Five SAMPs showed an inhibitory effect (MIC) on growth at low concentrations. Fluorescence microscope (FM) revealed that SAMPs induced 6-kDa pores in the membrane. Inhibitory assays in the presence of ergosterol revealed that some peptides lost their activity, suggesting interaction with it. Furthermore, FM analysis revealed that SAMPs induced caspase 3/7-mediated apoptosis and DNA degradation in cells. Scanning Electron Microscopy (SEM) analysis revealed that peptides induced many morphological alterations such as cell membrane, wall damage, and loss of internal content on cells. Our results strongly suggest synthetic peptides are potential alternative molecules to control growth and treat the cryptococcal infection.

摘要

是一种人类致病性酵母,主要导致免疫功能低下患者发生肺炎和脑膜炎。由其引起的感染是全球健康问题。合成抗菌肽(SAMPs)已成为应对真菌感染(包括由其引起的感染)的替代分子。在此,测试了八种SAMPs对其的抗真菌潜力,并通过荧光和扫描电子显微镜阐明了它们的作用机制。五种SAMPs在低浓度下对其生长表现出抑制作用(MIC)。荧光显微镜(FM)显示SAMPs在其细胞膜上诱导形成6 kDa的孔。在麦角固醇存在下的抑制试验表明,一些肽失去了活性,提示与麦角固醇相互作用。此外,FM分析显示SAMPs在其细胞中诱导了caspase 3/7介导的凋亡和DNA降解。扫描电子显微镜(SEM)分析显示,肽在其细胞上诱导了许多形态学改变,如细胞膜、细胞壁损伤以及内部内容物丧失。我们的结果有力地表明,合成肽是控制其生长和治疗隐球菌感染的潜在替代分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31e5/9416200/155316be1986/pharmaceutics-14-01678-g001.jpg

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