College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China; College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, China.
College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China; Faculty of Veterinary Medicine, Sumy National Agrarian University, Sumy, Ukraine.
Vet Microbiol. 2020 Apr;243:108634. doi: 10.1016/j.vetmic.2020.108634. Epub 2020 Mar 3.
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 Ca, 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.
胸膜肺炎放线杆菌是一种高度传染性和致命性呼吸道感染的病原体，给全球养猪业造成了巨大的经济损失。由于抗生素耐药性的增加，迫切需要寻找新的抗生素替代品来治疗胸膜肺炎放线杆菌感染。MPX 来源于黄蜂毒液，对多种细菌具有杀伤作用。本研究发现，MPX 对胸膜肺炎放线杆菌有较好的杀伤作用，最小抑菌浓度（MIC）为 16 μg/mL。MPX（1×MIC）处理 1 h 后，胸膜肺炎放线杆菌的细菌密度下降了 1000 倍，抗菌活性不受 pH 值或温度的影响。荧光显微镜观察显示，MPX（1×MIC）处理 0.5 h 后破坏细菌细胞膜，增加膜通透性并释放细菌蛋白和 Ca、Na 等阳离子。此外，MPX（1×MIC）处理显著减少了细菌生物膜的形成。定量 RT-PCR 结果显示，MPX 处理显著上调了 PurC 毒力基因的表达，下调了 ApxI、ApxII 和 Apa1 的表达。此外，发现 SapA 基因在胸膜肺炎放线杆菌对抗生素肽的耐受中发挥重要作用。在小鼠模型中的治疗评估表明，MPX 可保护小鼠免受致死剂量的胸膜肺炎放线杆菌感染，并缓解肺部炎症。本研究报告了使用 MPX 治疗胸膜肺炎放线杆菌感染，为开发治疗细菌感染的新药奠定了基础。
