Wang Lei, Zhao Xueqin, Zhu Chunling, Xia Xiaojing, Qin Wanhai, Li Mei, Wang Tongzhao, Chen Shijun, Xu Yanzhao, Hang Bolin, Sun Yawei, Jiang Jinqing, Richard Langford Paul, Lei Liancheng, Zhang Gaiping, Hu Jianhe
Postdoctoral Research Base, Henan Institute of Science and Technology, Xinxiang 453003, China; 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, P. R.China.
College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China.
Vet Microbiol. 2017 May;203:202-210. doi: 10.1016/j.vetmic.2017.02.021. Epub 2017 Mar 12.
Actinobacillus pleuropneumoniae is the causative agent of the highly contagious and deadly respiratory infection porcine pleuropneumonia, resulting in serious losses to the pig industry worldwide. Alternative to antibiotics are urgently needed due to the serious increase in antimicrobial resistance. Thymol is a monoterpene phenol and efficiently kills a variety of bacteria. This study found that thymol has strong bactericidal effects on the A. pleuropneumoniae 5b serotype strain, an epidemic strain in China. Sterilization occurred rapidly, and the minimum inhibitory concentration (MIC) is 31.25μg/mL; the A. pleuropneumoniae density was reduced 1000 times within 10min following treatment with 1 MIC. Transmission electron microscopy (TEM) analysis revealed that thymol could rapidly disrupt the cell walls and cell membranes of A. pleuropneumoniae, causing leakage of cell contents and cell death. In addition, treatment with thymol at 0.5 MIC significantly reduced the biofilm formation of A. pleuropneumoniae. Quantitative RT-PCR results indicated that thymol treatment significantly increased the expression of the virulence genes purC, tbpB1 and clpP and down-regulated ApxI, ApxII and Apa1 expression in A. pleuropneumoniae. Therapeutic analysis of a murine model showed that thymol (20mg/kg) protected mice from a lethal dose of A. pleuropneumoniae, attenuated lung pathological lesions. This study is the first to report the use of thymol to treat A. pleuropneumoniae infection, establishing a foundation for the development of new antimicrobials.
胸膜肺炎放线杆菌是高度传染性和致命性呼吸道感染猪胸膜肺炎的病原体，给全球养猪业造成严重损失。由于抗菌药物耐药性的严重增加，迫切需要抗生素的替代品。百里香酚是一种单萜酚，能有效杀死多种细菌。本研究发现，百里香酚对中国流行菌株胸膜肺炎放线杆菌5b血清型菌株具有很强的杀菌作用。杀菌迅速，最低抑菌浓度（MIC）为31.25μg/mL；用1倍MIC处理后10分钟内，胸膜肺炎放线杆菌密度降低1000倍。透射电子显微镜（TEM）分析表明，百里香酚可迅速破坏胸膜肺炎放线杆菌的细胞壁和细胞膜，导致细胞内容物泄漏和细胞死亡。此外，用0.5倍MIC的百里香酚处理可显著降低胸膜肺炎放线杆菌的生物膜形成。定量RT-PCR结果表明，百里香酚处理显著增加了胸膜肺炎放线杆菌中毒力基因purC、tbpB1和clpP的表达，并下调了ApxI、ApxII和Apa1的表达。小鼠模型的治疗分析表明，百里香酚（20mg/kg）可保护小鼠免受致死剂量的胸膜肺炎放线杆菌感染，减轻肺部病理损伤。本研究首次报道了使用百里香酚治疗胸膜肺炎放线杆菌感染，为开发新型抗菌药物奠定了基础。
