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评估氟尿苷对……的抗菌和抗毒力活性

Evaluating the Antibacterial and Antivirulence Activities of Floxuridine against .

作者信息

Li Jie, Han Ning, Li Yangyang, Zhao Feifei, Xiong Wenguang, Zeng Zhenling

机构信息

Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

出版信息

Int J Mol Sci. 2023 Sep 18;24(18):14211. doi: 10.3390/ijms241814211.

Abstract

is an emerging zoonotic pathogen that can cause fatal diseases such as meningitis and sepsis in pigs and human beings. The overuse of antibiotics is leading to an increased level of resistance in , and novel antimicrobial agents or anti-virulence agents for the treatment of infections caused by are urgently needed. In the present study, we investigated the antibacterial activity, mode of action and anti-virulence effects of floxuridine against . Floxuridine showed excessive antibacterial activity against both in vivo and in vitro; 4 × MIC of floxuridine could kill within 8 h in a time-kill assay. Meanwhile, floxuridine disrupted the membrane structure and permeability of the cytoplasmic membrane. Molecular docking revealed that floxuridine and SLY can be directly bind to each other. Moreover, floxuridine effectively inhibited the hemolytic capacity and expression levels of the virulence-related genes of . Collectively, these results indicate that the FDA-approved anticancer drug floxuridine is a promising agent and a potential virulence inhibitor against .

摘要

是一种新兴的人畜共患病原体,可在猪和人类中引起致命疾病,如脑膜炎和败血症。抗生素的过度使用导致其耐药性水平上升,迫切需要新型抗菌剂或抗毒力剂来治疗由其引起的感染。在本研究中,我们研究了氟尿苷对的抗菌活性、作用方式和抗毒力作用。氟尿苷在体内和体外均对显示出强大的抗菌活性;在时间杀菌试验中,4倍MIC的氟尿苷可在8小时内杀死。同时,氟尿苷破坏了细胞膜的膜结构和通透性。分子对接显示氟尿苷和SLY可以直接相互结合。此外,氟尿苷有效抑制了的溶血能力和毒力相关基因的表达水平。总的来说,这些结果表明,美国食品药品监督管理局批准的抗癌药物氟尿苷是一种有前途的药物,也是一种潜在的抗毒力抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309f/10532271/bebc1b77c71e/ijms-24-14211-g001.jpg

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