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抗菌肽 Jelleine-I 的多重作用机制及其体内抗菌功效。

Multiple action mechanism and in vivo antimicrobial efficacy of antimicrobial peptide Jelleine-I.

机构信息

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Research Unit of Peptide Science of Chinese Academy of Medical Sciences 2019RU066, Lanzhou University, West Donggang Road, 199, Lanzhou, 730000, China.

School/Hospital of Stomatology, Lanzhou University, West Donggang Road 199, Lanzhou, 730000, China.

出版信息

J Pept Sci. 2021 Mar;27(3):e3294. doi: 10.1002/psc.3294. Epub 2020 Dec 6.

DOI:10.1002/psc.3294
PMID:33283388
Abstract

With the extensive use of antibiotics in medicine, agriculture and food chemistry, the emergence of multi-drug resistant bacteria become more and more frequent and posed great threats to human health and life. So novel antimicrobial agents were urgently needed to defend the resistant bacteria. Jelleine-I was a small antimicrobial peptide (AMP) with eight amino acids in its sequence. It was believed to be an ideal template for developing antimicrobial agents. In the present study, the possible action mode against both gram-negative bacteria and gram-positive bacteria and in vivo antimicrobial activity was explored. Our results showed that Jelleine-I exhibits its antimicrobial activity mainly by disrupting the integrity of the cell membrane, which would not be affected by the conventional resistant mechanism. It also aims at some intracellular targets such as genomic DNA to inhibit the growth of microbes. In addition, the result of in vivo antimicrobial activity experiment showed that Jelleine-I performed a good therapeutic effect toward the mice with Escherichia coli infected peritonitis. Notably, Jelleine-I has negligible cytotoxicity toward the tested mammalian cells, indicating excellent cell selectivity between prokaryotic cells and eurkayotic cells. In summary, our results showed that Jelleine-I would be a potential candidate to be developed as a novel antimicrobial agent.

摘要

随着抗生素在医学、农业和食品化学中的广泛应用,越来越多的多药耐药菌出现,对人类健康和生命构成了巨大威胁。因此,迫切需要新型抗菌药物来对抗耐药菌。Jelleine-I 是一种含有 8 个氨基酸的小抗菌肽(AMP)。它被认为是开发抗菌药物的理想模板。在本研究中,探索了其针对革兰氏阴性菌和革兰氏阳性菌的可能作用模式和体内抗菌活性。研究结果表明,Jelleine-I 主要通过破坏细胞膜的完整性发挥其抗菌活性,而不受传统耐药机制的影响。它还针对一些细胞内靶标,如基因组 DNA,以抑制微生物的生长。此外,体内抗菌活性实验结果表明,Jelleine-I 对患有大肠杆菌感染性腹膜炎的小鼠具有良好的治疗效果。值得注意的是,Jelleine-I 对测试的哺乳动物细胞几乎没有细胞毒性,表明其在原核细胞和真核细胞之间具有优异的细胞选择性。综上所述,我们的研究结果表明,Jelleine-I 可能成为一种新型抗菌药物的候选药物。

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