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海洋肽-N6NH2及其衍生物-GUON6NH2对细胞内……具有强大的抗菌活性。 （原文此处不完整）

Marine Peptide-N6NH2 and Its Derivative-GUON6NH2 Have Potent Antimicrobial Activity Against Intracellular and .

作者信息

Han Huihui, Teng Da, Mao Ruoyu, Hao Ya, Yang Na, Wang Zhenlong, Li Ting, Wang Xiumin, Wang Jianhua

机构信息

Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China.

Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing, China.

出版信息

Front Microbiol. 2021 Mar 9;12:637427. doi: 10.3389/fmicb.2021.637427. eCollection 2021.

DOI:10.3389/fmicb.2021.637427
PMID:33767681
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7985170/
Abstract

is a facultative intracellular pathogen in humans and animals. There is no effective way except vaccine candidates to eradicate intracellular . In this study, four derivatives of marine peptide-N6NH2 were designed by an introduction of unnatural residues or substitution of natural ones, and their intracellular activities against were evaluated in macrophages and in mice, respectively. The minimum inhibitory concentration (MIC) value of N6NH2 and GUON6NH2 against was 8 μg/mL. GUON6NH2 showed higher stability to trypsin, lower toxicity (<1%) and longer post-antibiotic effect (PAE) than N6NH2 and other derivatives. Antibacterial mechanism results showed that GUON6NH2 could bind to LPS and destroyed outer/inner cell membranes of , superior to N6NH2 and norfloxacin. Both N6NH2 and GUON6NH2 were internalized into macrophages mainly via lipid rafts, micropinocytosis, and microtubule polymerization, respectively, and distributed in the cytoplasm. The intracellular inhibition rate of GUON6NH2 against was 97.05-100%, higher than that in case of N6NH2 (96.82-100%). In the -induced peritonitis mouse model, after treatment with of 1 μmol/kg N6NH2 and GUON6NH2, intracellular bacterial numbers were reduced by 1.54- and 1.97-Log CFU, respectively, higher than norfloxacin (0.35-Log CFU). These results suggest that GUON6NH2 may be an excellent candidate for novel antimicrobial agents to treat infectious diseases caused by intracellular

摘要

是人和动物中的兼性细胞内病原体。除了候选疫苗外，没有有效的方法根除细胞内的 。在本研究中，通过引入非天然残基或取代天然残基设计了四种海洋肽 -N6NH2 的衍生物，并分别在巨噬细胞和小鼠中评估了它们对 的细胞内活性。N6NH2 和 GUON6NH2 对 的最低抑菌浓度（MIC）值为 8 μg/mL。与 N6NH2 和其他衍生物相比，GUON6NH2 对胰蛋白酶表现出更高的稳定性、更低的毒性（<1%）和更长的抗生素后效应（PAE）。抗菌机制结果表明，GUON6NH2 可以与 LPS 结合并破坏 的外/内膜，优于 N6NH2 和诺氟沙星。N6NH2 和 GUON6NH2 分别主要通过脂筏、微胞饮作用和微管聚合内化到巨噬细胞中，并分布在细胞质中。GUON6NH2 对 的细胞内抑制率为 97.05 - 100%，高于 N6NH2 的情况（96.82 - 100%）。在 诱导的腹膜炎小鼠模型中，用 1 μmol/kg 的 N6NH2 和 GUON6NH2 处理后，细胞内细菌数量分别减少了 1.54 和 1.97 Log CFU，高于诺氟沙星（0.35 Log CFU）。这些结果表明，GUON6NH2 可能是治疗由细胞内 引起的传染病的新型抗菌剂的优秀候选物

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/b5c10a32c5f4/fmicb-12-637427-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/f67fcd036b82/fmicb-12-637427-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/c40d667189e8/fmicb-12-637427-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/ccc7267afee5/fmicb-12-637427-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/3929a3861632/fmicb-12-637427-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/89af0aa9d569/fmicb-12-637427-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/8386057ee408/fmicb-12-637427-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/b5c10a32c5f4/fmicb-12-637427-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/f67fcd036b82/fmicb-12-637427-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/c40d667189e8/fmicb-12-637427-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/ccc7267afee5/fmicb-12-637427-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/3929a3861632/fmicb-12-637427-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/89af0aa9d569/fmicb-12-637427-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/8386057ee408/fmicb-12-637427-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d78/7985170/b5c10a32c5f4/fmicb-12-637427-g007.jpg

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