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协同作用、提高细胞选择性和阐明抗菌肽 YS12 的作用机制。

Synergistic Effect, Improved Cell Selectivity, and Elucidating the Action Mechanism of Antimicrobial Peptide YS12.

机构信息

Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju 61452, Republic of Korea.

Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Aug 31;24(17):13522. doi: 10.3390/ijms241713522.

DOI:10.3390/ijms241713522
PMID:37686328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10487915/
Abstract

Antimicrobial peptides (AMPs) have attracted considerable attention as potential substitutes for traditional antibiotics. In our previous research, a novel antimicrobial peptide YS12 derived from the strain showed broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria. In this study, the fractional inhibitory concentration index (FICI) indicated that combining YS12 with commercial antibiotics produced a synergistic effect. Following these findings, the combination of YS12 with an antibiotic resulted in a faster killing effect against bacterial strains compared to the treatment with the peptide YS12 or antibiotic alone. The peptide YS12 maintained its antimicrobial activity under different physiological salts (Na, Mg, and Fe). Most importantly, YS12 exhibited no cytotoxicity towards Raw 264.7 cells and showed low hemolytic activity, whereas positive control melittin indicated extremely high toxicity. In terms of mode of action, we found that peptide YS12 was able to bind with LPS through electrostatic interaction. The results from fluorescent measurement revealed that peptide YS12 damaged the integrity of the bacterial membrane. Confocal laser microscopy further confirmed that the localization of peptide YS12 was almost in the cytoplasm of the cells. Peptide YS12 also exhibited anti-inflammatory activity by reducing the release of LPS-induced pro-inflammatory mediators such as TNF-α, IL-1β, and NO. Collectively, these properties strongly suggest that the antimicrobial peptide YS12 may be a promising candidate for treating microbial infections and inflammation.

摘要

抗菌肽(AMPs)作为传统抗生素的潜在替代品引起了广泛关注。在我们之前的研究中,一种新型抗菌肽 YS12 来源于 菌株,对革兰氏阳性和革兰氏阴性细菌表现出广谱抗菌活性。在这项研究中,部分抑菌浓度指数(FICI)表明,YS12 与商业抗生素联合使用具有协同作用。基于这些发现,YS12 与抗生素的联合使用对细菌菌株产生了比单独使用肽 YS12 或抗生素更快的杀伤作用。肽 YS12 在不同生理盐(Na、Mg 和 Fe)下保持其抗菌活性。最重要的是,YS12 对 Raw 264.7 细胞没有细胞毒性,并且溶血活性低,而阳性对照蜂毒素则表现出极高的毒性。就作用方式而言,我们发现肽 YS12 能够通过静电相互作用与 LPS 结合。荧光测量的结果表明,肽 YS12 破坏了细菌膜的完整性。共聚焦激光显微镜进一步证实,肽 YS12 的定位几乎在细胞的细胞质中。肽 YS12 还通过减少 LPS 诱导的促炎介质(如 TNF-α、IL-1β 和 NO)的释放表现出抗炎活性。总的来说,这些特性强烈表明抗菌肽 YS12 可能是治疗微生物感染和炎症的有前途的候选药物。

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