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LC-AMP-I1,一种源自狼蛛毒液的新型抗菌肽。

LC-AMP-I1, a novel venom-derived antimicrobial peptide from the wolf spider .

作者信息

Wang Junyao, Liu Xi, Song Yuxin, Liu Zhonghua, Tang Xing, Tan Huaxin

机构信息

Institute of Biochemistry and Molecular Biology, Hengyang Medical College, University of South China, Hengyang, China.

The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.

出版信息

Antimicrob Agents Chemother. 2025 Jan 31;69(1):e0042424. doi: 10.1128/aac.00424-24. Epub 2024 Dec 2.

Abstract

Antibiotic resistance has become a critical concern in recent years, and antimicrobial peptides may function as innovative antibacterial agents to address this issue. In this work, we identified a novel antimicrobial peptide, LC-AMP-I1, derived from the venom of , demonstrating substantial antibacterial properties and minimal hemolytic activity. LC-AMP-I1 was subjected to additional assessment for antibacterial efficacy, anti-biofilm properties, drug resistance, stability, and cytotoxicity . It exhibited comparable antibacterial efficacy to melittin against six common clinical multidrug-resistant bacteria, effectively inhibiting biofilm formation and disrupting established biofilms. Additionally, LC-AMP-I1 demonstrated minimal bacterial resistance, excellent stability, negligible mammalian cell toxicity, low hemolytic activity, and appropriate selectivity for both normal and tumor cells. When combined with traditional antibiotics, LC-AMP-I1 exhibited additive or synergistic therapeutic effects. In a neutropenic mouse thigh infection model, LC-AMP-I1 exhibited a therapeutic effect in inhibiting bacterial proliferation . The mechanistic investigation indicated that LC-AMP-I1 could influence bacterial cell membrane permeability at low concentrations and directly disrupt structure-function at high concentrations. The results of this work indicate that LC-AMP-I1 may function as a viable alternative to traditional antibiotics in addressing multidrug-resistant bacteria.

摘要

近年来,抗生素耐药性已成为一个关键问题,抗菌肽可能作为创新的抗菌剂来解决这一问题。在这项研究中,我们鉴定了一种源自[具体来源]毒液的新型抗菌肽LC-AMP-I1,它具有显著的抗菌特性和最小的溶血活性。对LC-AMP-I1进行了抗菌效果、抗生物膜特性、耐药性、稳定性和细胞毒性的额外评估。它对六种常见临床多重耐药菌的抗菌效果与蜂毒肽相当,能有效抑制生物膜形成并破坏已形成的生物膜。此外,LC-AMP-I1表现出最小的细菌耐药性、出色的稳定性、可忽略不计的哺乳动物细胞毒性、低溶血活性以及对正常细胞和肿瘤细胞的适当选择性。与传统抗生素联合使用时,LC-AMP-I1表现出相加或协同的治疗效果。在中性粒细胞减少小鼠大腿感染模型中,LC-AMP-I1表现出抑制细菌增殖的治疗效果。机制研究表明,LC-AMP-I1在低浓度时可影响细菌细胞膜通透性,在高浓度时可直接破坏结构功能。这项研究的结果表明,在应对多重耐药菌方面,LC-AMP-I1可能成为传统抗生素的可行替代品。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7b/11784185/3d03903f9aef/aac.00424-24.f001.jpg

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