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异丙氧基苯胍对……的抗菌活性

Antibacterial activity of isopropoxy benzene guanidine against .

作者信息

Lu Yixing, Qiao Weimei, Xue Yaqian, Hong Xiaoxin, Jin Yuhang, Li Jie, Peng Xianfeng, Zeng Dongping, 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, China.

National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, Guangzhou, China.

出版信息

Front Pharmacol. 2024 Feb 2;15:1347250. doi: 10.3389/fphar.2024.1347250. eCollection 2024.

Abstract

is an important pathogen in waterfowl, leading to substantial economic losses. In recent years, there has been a notable escalation in the drug resistance rate of Consequently, there is an imperative need to expedite the development of novel antibacterial medications to effectively manage the infection caused by . This study investigated the and antibacterial activities of a novel substituted benzene guanidine analog, namely, isopropoxy benzene guanidine (IBG), against by using the microdilution method, time-killing curve, and a pericarditis model. The possible mechanisms of these activities were explored. The minimal inhibitory concentration (MIC) range of IBG for was 0.5-2 μg/mL. Time-killing curves showed a concentration-dependent antibacterial effect. IBG alone or in combination with gentamicin significantly reduced the bacterial load of in the pericarditis model. Serial-passage mutagenicity assays showed a low probability for developing IBG resistance. Mechanistic studies suggested that IBG induced membrane damage by binding to phosphatidylglycerol and cardiolipin, leading to an imbalance in membrane potential and the transmembrane proton gradient, as well as the decreased of intracellular adenosine triphosphate. In summary, IBG is a potential antibacterial for controlling infections.

摘要

是水禽中的一种重要病原体,会导致巨大的经济损失。近年来,其耐药率显著上升。因此,迫切需要加快新型抗菌药物的研发,以有效控制由其引起的感染。本研究采用微量稀释法、时间杀菌曲线和心包炎模型,研究了一种新型取代苯胍类似物异丙氧基苯胍(IBG)对的体外抗菌活性和体内抗菌活性,并探讨了这些活性的可能机制。IBG对的最低抑菌浓度(MIC)范围为0.5-2μg/mL。时间杀菌曲线显示出浓度依赖性抗菌作用。在心包炎模型中,单独使用IBG或与庆大霉素联合使用均能显著降低的细菌载量。连续传代致突变试验表明,产生IBG耐药性的可能性较低。机制研究表明,IBG通过与磷脂酰甘油和心磷脂结合诱导膜损伤,导致膜电位和跨膜质子梯度失衡,以及细胞内三磷酸腺苷减少。总之,IBG是一种控制感染的潜在抗菌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9810/10870170/50858187d71f/fphar-15-1347250-g001.jpg

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