【摘要】 目的：筛选中药活性成分作为鼠伤寒沙门氏菌致病性岛III(Salmonella pathogenicity island III,SPI-3)潜在毒力抑制剂。方法：通过分子对接技术明确中药成分与SPI-3中的Mgt C蛋白的潜在结合关系。使用β-半乳糖苷酶测定法评估中药成分对mgt C转录的影响。最后，通过评估细菌生长曲线和关键代谢基因的转录水平研究药物对细菌生长的影响。结果：所有27个候选中药成分均显示出与Mgt C结合的潜力。阿魏酸、对羟基肉桂酸、牛蒡子苷和掌叶防己碱使mgt C的转录活性降低了15%以上。这四个成分对mgt C转录的最低抑制浓度分别为：阿魏酸16μM；对羟基肉桂酸40μM；牛蒡子苷80μM；掌叶防己碱160μM。此外，我们证实这四种成分均未抑制细菌生长。结论：在本研究中，我们建立了一种基于β-半乳糖苷酶测定法的鼠伤寒沙门氏菌毒力抑制剂筛选方法。以SPI-3为靶标，筛选了27种中药成分，发现有4种对鼠伤寒沙门氏菌毒力具有潜在的强效抑制作用。这为未来从草药中开发新型抗生素提供了先导化合物。这种方法也可用于筛选其他致病菌的毒力抑制剂。更多还原

【Abstract】 Objective: To screen active constituents of traditional Chinese medicines(TCMs) as potential virulence inhibitors of Salmonella pathogenicity island III(SPI-3).Methods: The potential binding of TCM constituents to the Mgt C protein of SPI-3 was clarified using molecular docking. The β-galactosidase assay was used to evaluate the effect of the TCM constituents on mgt C transcription. Finally, the effect of the drug on bacterial growth was investigated by assessing the growth curves and transcription levels of the key metabolic genes.Results: All 27 candidate TCM constituents showed that they could potentially bind to Mgt C. The addition of ferulic acid, p-hydroxycinnamic acid, arctiin, and palmatine resulted in a more than 15% reduction in the transcriptional activity of mgt C. The minimum inhibitory concentrations of those four constituents on mgt C transcription were as follows: ferulic acid, 16 μM; p-hydroxycinnamic acid, 40 μM; arctiin,80 μM; and palmatine, 160 μM. Additionally, we confirmed that none of these four constituents inhibited bacterial growth.Conclusion: In this study, we established a screening method for Salmonella virulence inhibitors based on the β-galactosidase assay, targeting SPI-3. Twenty-seven TCM constituents were screened, and four were found to have potentially potent inhibitory effects on Salmonella virulence. This provides lead compounds from herbal medicines for the development of novel antibiotics in the future. This method can also be used to screen for the virulence inhibitors of other pathogenic bacteria.更多还原