Temporin-Derived Peptides Protect Mice against Enterohemorrhagic Escherichia coli O157:H7 Infection by Inhibiting Inflammation and Enhancing the Intestinal Epithelial Barrier

IF 4.5 2区医学 Q2 CHEMISTRY, MEDICINAL

ACS Infectious Diseases Pub Date : 2026-08-14 Epub Date: 2026-07-08 DOI:10.1021/acsinfecdis.6c00158

Jing Chen, Ruiying Zhu, Shangjun Jiang, Zhiju Xue, Wenhuan Deng, Yining Wang, Shuangshuang Wei, Junchen Lyu, Wenting Hu, Yanting Song, Rong Wang, Yingxia Zhang

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引用次数: 0

Abstract

Intestinal inflammation can destroy the integrity of the intestinal barrier and disrupt immune homeostasis, increasing the risks of developing fatal diseases. Enterohemorrhagic Escherichia coli (EHEC) O157:H7, a prominent pathogen primarily transmitted through contaminated food, is known to trigger intestinal inflammation and subsequent infections. Temporin-GHbK (GHbK) and temporin-GHb3K (GHb3K), derived from temporin-GHb of Hylarana guentheri, were synthesized and demonstrated antimicrobial and anti-biofilm activities against EHEC in vitro. They also exhibited efficacy in preventing EHEC infection in vivo. GHbK and GHb3K significantly decreased the disease activity index (DAI) in EHEC-infected mice in comparison with the untreated model group. The derived peptides exhibited barrier-protective effects by preserving structural integrity, reducing inflammatory infiltrates in the intestinal epithelium, and maintaining gut microbiota diversity. Taken together, GHbK and GHb3K exhibit promising anti-inflammatory and anti-infection potential against EHEC infection. These findings lay a foundation for exploring the application of antibacterial peptides in the treatment of EHEC infection.

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颞叶肽通过抑制炎症和增强肠上皮屏障保护小鼠免受肠出血性大肠杆菌O157:H7感染

肠道炎症可以破坏肠道屏障的完整性，破坏免疫稳态，增加患致命疾病的风险。肠出血性大肠杆菌（EHEC） O157:H7是一种主要通过受污染的食物传播的主要病原体，已知可引发肠道炎症和随后的感染。本文合成了从黄刺海拉鱼（Hylarana guentheri）中提取的Temporin-GHbK （GHbK）和temporin-GHb3K (GHb3K)，并在体外对肠出血性大肠杆菌（EHEC）具有抗菌和抗生物膜活性。它们在体内也显示出预防肠出血性大肠杆菌感染的功效。与未治疗模型组相比，GHbK和GHb3K显著降低ehec感染小鼠的疾病活动指数（DAI）。衍生肽通过保持结构完整性、减少肠上皮炎症浸润和维持肠道微生物群多样性，显示出屏障保护作用。综上所述，GHbK和GHb3K对肠出血性大肠杆菌感染具有良好的抗炎和抗感染潜力。这些发现为探索抗菌肽在肠出血性大肠杆菌感染治疗中的应用奠定了基础。

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来源期刊

ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES

CiteScore

9.70

自引率

3.80%

发文量

213

期刊介绍： ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.