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Mo-CBP3-PepI, Mo-CBP3-PepII, and Mo-CBP3-PepIII are synthetic antimicrobial peptides active against human pathogens by stimulating ROS generation and increasing plasma membrane permeability
Biochimie ( IF 3.3 ) Pub Date : 2018-10-31 , DOI: 10.1016/j.biochi.2018.10.016
Jose T.A. Oliveira , Pedro F.N. Souza , Ilka M. Vasconcelos , Lucas P. Dias , Thiago F. Martins , Mauricio F. Van Tilburg , Maria I.F. Guedes , Daniele O.B. Sousa

The efficiency of current antimicrobial drugs is noticeably decreasing and thus the development of new treatments is necessary. Natural and synthetic antimicrobial peptides (AMPs) have attracted great attention as promising candidates. Inspired on Mo-CBP3, an antimicrobial protein from Moringa oleifera seeds, we designed and synthesized three AMPs named Mo-CBP3-PepI, Mo-CBP3-PepII, and Mo-CBP3-PepIII. All these three peptides inhibited the growth of Candida species and pathogenic bacteria, penetrate into microbial cells, but none is hemolytic or toxic to human cells. Mo-CBP3-PepIII, particularly, showed the strongest antimicrobial activity against Staphylococcus aureus and Candida species, important human pathogens. Additionally, Mo-CBP3-PepIII did not exhibit hemolytic or toxic activity to mammalian cells, but increased Staphylococcus aureus plasma membrane permeabilization. In Candida parapsilosis, Mo-CBP3-PepIII induced pore formation in the plasma membrane and overproduction of reactive oxygen species. Bioinformatics analysis suggested that Mo-CBP3-PepIII is resistant to pepsin digestion and other proteolytic enzymes present in the intestinal environment, which opens the possibility of oral delivery in future treatments. Together, these results suggest that Mo-CBP3-PepIII has great potential as an antimicrobial agent against the bacterium S. aureus and the fungi C. parapsilosis.



中文翻译:

Mo -CBP 3 -PepI,Mo -CBP 3 -PepII和Mo -CBP 3 -PepIII是通过刺激ROS产生和增加质膜通透性而对人类病原体具有活性的合成抗菌肽

当前抗微生物药物的效率明显下降,因此有必要开发新的治疗方法。天然和合成的抗菌肽(AMPs)作为有前途的候选物已引起了极大的关注。受到来自辣木种子的抗菌蛋白Mo -CBP 3的启发,我们设计并合成了三种名为Mo- CBP 3 -PepI,Mo- CBP 3 -PepII和Mo- CBP 3 -PepIII的AMP。所有这三种肽均抑制念珠菌和病原菌的生长,渗透到微生物细胞中,但没有一种对人体细胞具有溶血作用或毒性。Mo- CBP 3 -PepIII特别显示出对金黄色葡萄球菌念珠菌(最重要的人类病原体)的最强抗菌活性。另外,Mo- CBP 3 -PepIII对哺乳动物细胞不表现出溶血或毒性活性,但是增加了金黄色葡萄球菌质膜通透性。在副念珠菌中Mo -CBP 3 -PepIII诱导了质膜中的孔形成和活性氧的过度产生。生物信息学分析表明,Mo -CBP 3-PepIII对肠道环境中存在的胃蛋白酶消化和其他蛋白水解酶具有抵抗力,这为将来的治疗提供了口服给药的可能性。总之,这些结果表明,Mo -CBP 3 -PepIII具有作为抗金黄色葡萄球菌和真菌C. parapsilosis的抗菌剂的巨大潜力

更新日期:2018-10-31
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