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The antimicrobial peptide MPX kills Actinobacillus pleuropneumoniae and reduces its pathogenicity in mice
Veterinary Microbiology ( IF 3.3 ) Pub Date : 2020-03-03 , DOI: 10.1016/j.vetmic.2020.108634
Lei Wang , Xueqin Zhao , Chunling Zhu , Yaya Zhao , Shuangshuang Liu , Xiaojing Xia , Xin Liu , Huihui Zhang , Yanzhao Xu , Bolin Hang , Yawei Sun , Shijun Chen , Jinqing Jiang , Yueyu Bai , Gaiping Zhang , Liancheng Lei , Langford Paul Richard , Hanna Fotina , Jianhe Hu

Actinobacillus pleuropneumoniae is the causative agent of highly contagious and fatal respiratory infections, causing substantial economic losses to the global pig industry. Due to increased antibiotic resistance, there is an urgent need to find new antibiotic alternatives for treating A. pleuropneumoniae infections. MPX is obtained from wasp venom and has a killing effect on various bacteria. This study found that MPX had a good killing effect on A. pleuropneumoniae and that the minimum inhibitory concentration (MIC) was 16 μg/mL. The bacterial density of A. pleuropneumoniae decreased 1000 times after MPX (1 × MIC) treatment for 1 h, and the antibacterial activity was not affected by pH or temperature. Fluorescence microscopy showed that MPX (1 × MIC) destroyed the bacterial cell membrane after treatment for 0.5 h, increasing membrane permeability and releasing bacterial proteins and Ca2+, Na+ and other cations. In addition, MPX (1 × MIC) treatment significantly reduced the formation of bacterial biofilms. Quantitative RT-PCR results showed that MPX treatment significantly upregulated the expression of the PurC virulence gene and downregulated that of ApxI, ApxII, and Apa1. In addition, the Sap A gene was found to play an important role in the tolerance of A. pleuropneumoniae to antimicrobial peptides. Therapeutic evaluation in a murine model showed that MPX protects mice from a lethal dose of A. pleuropneumoniae and relieves lung inflammation. This study reports the use of MPX to treat A. pleuropneumonia infections, laying the foundation for the development of new drugs for bacterial infections.



中文翻译:

抗菌肽MPX可杀死胸膜肺炎放线杆菌并降低其在小鼠中的致病性

胸膜肺炎放线杆菌是高度传染性和致命性呼吸道感染的病原体,对全球养猪业造成重大经济损失。由于增加的抗生素抗性,迫切需要寻找新的抗生素替代品来治疗胸膜肺炎链球菌感染。MPX是从黄蜂毒液中获得的,对多种细菌具有杀灭作用。这项研究发现MPX对胸膜肺炎链球菌具有良好的杀灭作用,最低抑菌浓度(MIC)为16μg/ mL。胸膜肺炎链球菌的细菌密度在MPX(1×MIC)处理1 h后下降了1000倍,并且抗菌活性不受pH或温度的影响。荧光显微镜显示,MPX(1×MIC)处理0.5 h后破坏了细菌细胞膜,增加了膜的通透性并释放出细菌蛋白和Ca 2 +,Na +和其他阳离子。此外,MPX(1×MIC)处理显着减少了细菌生物膜的形成。定量RT-PCR结果表明,MPX处理显着上调了PurC毒力基因的表达,而下调了ApxI,ApxII和Apa1的表达。另外,发现Sap A基因在胸膜肺炎放线杆菌的耐受中起重要作用抗菌肽。在鼠模型中的治疗评估表明,MPX可保护小鼠免受致命剂量的胸膜肺炎放线杆菌的侵害并减轻肺部炎症。这项研究报告了使用MPX来治疗胸膜肺炎支原体感染,为细菌感染新药的开发奠定了基础。

更新日期:2020-03-20
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