A Novel Antimicrobial Peptide Sparamosin(26-54) From the Mud Crab Scylla paramamosain Showing Potent Antifungal Activity Against Cryptococcus neoformans.
A Novel Antimicrobial Peptide Sparamosin(26-54) From the Mud Crab Scylla paramamosain Showing Potent Antifungal Activity Against Cryptococcus neoformans.
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DOI：
10.3389/fmicb.2021.746006
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发表时间：
2021
影响因子：
5.2
通讯作者：
Wang KJ
中科院分区：
文献类型：
--
作者：
Chen YC;Yang Y;Zhang C;Chen HY;Chen F;Wang KJ
由于耐药真菌的日益流行和目前治疗真菌感染的策略的局限性，探索和开发新的抗真菌药物或替代药物是必要的。本研究在泥蟹Scylla paramamosain中鉴定出一种新的抗菌肽，名为Sparamosin，该肽含有22个氨基酸的信号肽和54个氨基酸的成熟肽。测定了其合成的成熟肽和两个截短肽（Sparamosin1-25和Sparamosin26-54）的抗菌活性。结果表明，Sparamosin26-54对多种革兰氏阴性菌、革兰氏阳性菌和真菌均有较强的杀伤活性，特别是具有快速的杀真菌动力学（10 min内杀死99%的新生隐球菌），对新生隐球菌具有较强的抗生物膜活性，但对哺乳动物细胞无细胞毒作用。RNA-seq结果显示，经Sparamosin26-54处理后，细胞壁组分生物合成、细胞壁完整性信号通路、抗氧化应激、细胞凋亡和DNA修复等相关基因的表达显著上调，表明Sparamosin26-54可能破坏新生C.细胞壁，引起氧化应激、DNA损伤和细胞凋亡。其基本机制得到进一步确认。电镜和染色观察发现，Sparamosin26-54能与细胞膜上的多种磷脂结合，通过破坏细胞壁和细胞膜的完整性，有效杀死新生弧菌。此外，研究发现，经Sparamosin26-54处理后，活性氧（ROS）积累增加，线粒体膜电位（MMP）被破坏，DNA片段化，这些都是细胞凋亡的标志。综上所述，Sparamosin26-54作为一种有效的抗菌药物具有良好的应用前景，特别是对新生梭状菌的感染。
Due to the increasing prevalence of drug-resistant fungi and the limitations of current treatment strategies to fungal infections, exploration and development of new antifungal drugs or substituents are necessary. In the study, a novel antimicrobial peptide, named Sparamosin, was identified in the mud crab Scylla paramamosain, which contains a signal peptide of 22 amino acids and a mature peptide of 54 amino acids. The antimicrobial activity of its synthetic mature peptide and two truncated peptides (Sparamosin1–25 and Sparamosin26–54) were determined. The results showed that Sparamosin26–54 had the strongest activity against a variety of Gram-negative bacteria, Gram-positive bacteria and fungi, in particular had rapid fungicidal kinetics (killed 99% Cryptococcus neoformans within 10 min) and had potent anti-biofilm activity against C. neoformans, but had no cytotoxic effect on mammalian cells. The RNA-seq results showed that after Sparamosin26–54 treatment, the expression of genes involved in cell wall component biosynthesis, cell wall integrity signaling pathway, anti-oxidative stress, apoptosis and DNA repair were significantly up-regulated, indicating that Sparamosin26–54 might disrupt the cell wall of C. neoformans, causing oxidative stress, DNA damage and cell apoptosis. The underlying mechanism was further confirmed. Sparamosin26–54 could bind to several phospholipids in the cell membrane and effectively killed C. neoformans through disrupting the integrity of the cell wall and cell membrane observed by electron microscope and staining assay. In addition, it was found that the accumulation of reactive oxygen species (ROS) increased, the mitochondrial membrane potential (MMP) was disrupted, and DNA fragmentation was induced after Sparamosin26–54 treatment, which are all hallmarks of apoptosis. Taken together, Sparamosin26–54 has a good application prospect as an effective antimicrobial agent, especially for C. neoformans infections.
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影响因子：
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作者：
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发表时间：
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期刊：
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影响因子：
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