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从锯缘青蟹中发现的一种新型抗菌肽 Scyreptin,在小鼠烧伤创面模型中对铜绿假单胞菌早期感染具有潜在的治疗作用。

A novel antimicrobial peptide Scyreptin from Scylla paramamosain exhibiting potential therapy of Pseudomonas aeruginosa early infection in a mouse burn wound model.

机构信息

State Key Laboratory of Marine Environmental Science, College of Ocean & Earth Sciences, Xiamen University, Xiamen, Fujian, China.

State Key Laboratory of Marine Environmental Science, College of Ocean & Earth Sciences, Xiamen University, Xiamen, Fujian, China; State-Province Joint Engineering Laboratory of Marine Bioproducts and Technology, College of Ocean & Earth Sciences, Xiamen University, Xiamen, Fujian, China.

出版信息

Biochem Pharmacol. 2023 Dec;218:115917. doi: 10.1016/j.bcp.2023.115917. Epub 2023 Nov 10.

DOI:10.1016/j.bcp.2023.115917
PMID:37952897
Abstract

Antimicrobial resistance (AMR) constitutes a significant global threat to human health. In recent years, there has been a concerning surge in infections caused by multidrug-resistant bacteria, highlighting the pressing need to urgently explore novel and effective alternatives to conventional antibiotics. Antimicrobial peptides (AMPs) have emerged as a focal point of research, capturing significant attention as promising antimicrobial agents. In this study, we have identified a novel cationic antimicrobial peptide (AMP) named Scyreptin, derived from the marine invertebrate Scylla paramamosain. The results showed that Scyreptin exhibits a broad-spectrum antimicrobial activity, demonstrating significant potency against both bacteria and fungi, and even against the clinically isolated multidrug-resistant bacteria Pseudomonas aeruginosa. Moreover, Scyreptin exhibited rapid bactericidal kinetic. The results of antibacterial mechanism showed that Scyreptin destroyed the integrity of bacterial membranes, leading to bacterial death and exhibited potent anti-biofilm activity against P. aeruginosa. The activity of Scyreptin against bacteria had a favorable thermal stability, displayed a certain ion tolerance, and showed no discernible cytotoxicity when assessed against both the mammalian cell line HEK293T and the fish cell lines ZF4. In an In vivo study, Scyreptin exhibited a remarkably reduction in the bacterial load caused by multidrug-resistant P. aeruginosa at the site of infection, and promoted wound healing in a mouse model of burn infection. This study indicated that Scyreptin holds promise as an effective antibacterial agent, potentially serving as a topical skin treatment against multidrug-resistant bacterial infections, including those caused by P. aeruginosa.

摘要

抗菌药物耐药性(AMR)对人类健康构成重大的全球性威胁。近年来,多药耐药菌引起的感染令人担忧地增加,突出表明迫切需要紧急探索新型和有效的替代传统抗生素。抗菌肽(AMPs)已成为研究焦点,作为有前途的抗菌剂引起了广泛关注。在这项研究中,我们从海洋无脊椎动物锯缘青蟹中发现了一种新型阳离子抗菌肽(AMP),命名为 Scyreptin。结果表明,Scyreptin 具有广谱抗菌活性,对细菌和真菌均具有显著的杀菌作用,甚至对临床分离的多药耐药菌铜绿假单胞菌也具有杀菌作用。此外,Scyreptin 具有快速杀菌动力学。抗菌机制的研究结果表明,Scyreptin 破坏了细菌膜的完整性,导致细菌死亡,并对铜绿假单胞菌表现出强大的抗生物膜活性。Scyreptin 对细菌的活性具有良好的热稳定性,表现出一定的离子耐受性,并且在哺乳动物细胞系 HEK293T 和鱼类细胞系 ZF4 中评估时没有明显的细胞毒性。在体内研究中,Scyreptin 显著降低了感染部位多药耐药铜绿假单胞菌引起的细菌负荷,并促进了烧伤感染小鼠模型的伤口愈合。这项研究表明,Scyreptin 有望成为一种有效的抗菌剂,可作为一种局部皮肤治疗多药耐药细菌感染的方法,包括由铜绿假单胞菌引起的感染。

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