Antimicrobial and anti-inflammatory activities of the neuropeptide antagonist SPA.
Antimicrobial and anti-inflammatory activities of the neuropeptide antagonist SPA.
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神经肽拮抗剂 SPA 的抗菌和抗炎活性。
DOI：
10.1002/psc.3402
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发表时间：
2022
影响因子：
2.1
通讯作者：
Zhang Wei
中科院分区：
文献类型：
--
作者：
Zhu Zhongwen;Yao Yufan;Huang Sujie;Ma Ling;Song Jingjing;Zhang Wei
由于抗生素耐药细菌的日益流行，抗菌肽受到越来越多的关注。然而，抗菌肽的临床应用开发仍然是一个巨大的挑战。SPA （[D‐rg1, D‐Trp5,7,9, Leu11]SP）是一种广谱神经肽拮抗剂，是P物质的类似物。在这项研究中，我们发现SPA可以通过膜破坏有效地杀死革兰氏阳性和革兰氏阴性细菌，类似于抗菌肽。此外，SPA对细菌的杀伤活性高于对哺乳动物细胞的杀伤活性。我们的研究结果还表明，SPA可以显著降低促炎细胞因子的表达，并挽救脂多糖（LPS）致死性脓毒性休克小鼠。本研究表明，SPA具有令人印象深刻的治疗潜力，使其成为开发有效抗生素的良好模板。同时，本研究为开发抗细菌感染的多功能治疗剂提供了新的思路。
Antimicrobial peptides have received increased attention due to the increasing prevalence of antibiotic‐resistant bacteria. However, the development of antimicrobial peptides for clinical applications remains a huge challenge. SPA ([D‐rg1, D‐Trp5,7,9, Leu11]SP), an analog of substance P, is a broad‐spectrum neuropeptide antagonist. In this study, we found that SPA could efficiently kill Gram‐positive and Gram‐negative bacteria by membrane disruption, similar to antimicrobial peptides. In addition, SPA showed high killing activity toward bacteria rather than mammalian cells. Our results also demonstrated that SPA could significantly decrease the expression of proinflammatory cytokines and rescue mice from lethal septic shock induced by lipopolysaccharide (LPS). The impressive therapeutic potential of SPA, as indicated in this study, makes it a good template for developing effective antibiotics. Meanwhile, our study provides a new idea for developing multifunctional therapeutic agents to combat bacterial infections.