Hua Xin, Yang Qin, Zhang Wanjiang, Dong Zhimin, Yu Shenye, Schwarz Stefan, Liu Siguo
Division of Bacterial Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Tianjin Animal Science and Veterinary Research Institute, Tianjin, China.
Front Pharmacol. 2018 Jun 13;9:619. doi: 10.3389/fphar.2018.00619. eCollection 2018.
This study aimed at investigating the antibacterial activity of aspidinol, an extract from (L.) Schott, against methicillin-resistant (MRSA). MRSA isolates were treated with aspidinol to determine the differential expression of genes and associated pathways following the drug treatment. Aspidinol displayed significant anti-MRSA activity, both (minimum inhibitory concentration = 2 μg/mL) and , and achieved an antibacterial effect comparable to that of vancomycin. In the lethal septicemic mouse study, a dose of 50 mg/kg of either aspidinol or vancomycin provided significant protection from mortality. In the non-lethal septicemic mouse study, aspidinol and vancomycin produced a significant reduction in mean bacterial load in murine organs, including the spleen, lung, and liver. After treatment with aspidinol, we found through RNA-seq and RT-PCR experiments that the inhibition of the formation of ribosomes was the primary cell-killing mechanism, and the inhibition of amino acid synthesis and the reduction of virulence factors might play a secondary role.
本研究旨在调查肖叶菝葜提取物白屈菜赤碱对耐甲氧西林金黄色葡萄球菌（MRSA）的抗菌活性。用白屈菜赤碱处理MRSA分离株，以确定药物处理后基因的差异表达及相关通路。白屈菜赤碱显示出显著的抗MRSA活性，无论是最低抑菌浓度（MIC = 2 μg/mL）还是最低杀菌浓度（MBC），并且实现了与万古霉素相当的抗菌效果。在致死性败血症小鼠研究中，50 mg/kg剂量的白屈菜赤碱或万古霉素均提供了显著的死亡保护。在非致死性败血症小鼠研究中，白屈菜赤碱和万古霉素使小鼠器官（包括脾脏、肺和肝脏）中的平均细菌载量显著降低。在用白屈菜赤碱处理后，我们通过RNA测序和逆转录聚合酶链反应实验发现，抑制核糖体形成是主要的细胞杀伤机制，抑制氨基酸合成和降低毒力因子可能起次要作用。
