A new coumarin compound DCH combats methicillin-resistant Staphylococcus aureus biofilm by targeting arginine repressor
A new coumarin compound DCH combats methicillin-resistant Staphylococcus aureus biofilm by targeting arginine repressor
复制标题
一种新型香豆素化合物 DCH 通过靶向精氨酸阻遏物对抗耐甲氧西林金黄色葡萄球菌生物膜
DOI：
10.1126/sciadv.aay9597
复制
发表时间：
2020-07-01
期刊：
影响因子：
13.6
通讯作者：
Li, Mingkai
中科院分区：
文献类型：
--
作者：
Qu, Di;Hou, Zheng;Li, Mingkai
香豆素类化合物DCH通过抑制细菌精氨酸阻遏物对抗耐甲氧西林金黄色葡萄球菌感染。金黄色葡萄球菌感染由于生物膜形成和抗生素耐药性而难以根除。耐甲氧西林金黄色葡萄球菌（MRSA）感染的日益普遍，需要开发一种新的抗细菌生物膜的药物。我们报告了一种新的香豆素化合物，称为DCH，有效地打击MRSA在体外和体内，并表现出强大的抗菌膜活性没有检测到的阻力。细胞蛋白质组分析表明，DCH的分子作用机制涉及精氨酸分解代谢途径。使用DCH的分子对接和结合亲和力测定，并比较野生型和ArgR缺陷型MRSA菌株的特性，我们证明精氨酸阻遏物ArgR，精氨酸分解代谢途径的重要调节剂，是DCH的目标。这些发现表明，DCH是一种有前途的先导化合物，并验证细菌ArgR作为开发抗MRSA生物膜新药的潜在靶点。
Coumarin compound DCH combats methicillin-resistant Staphylococcus aureus infection via inhibiting bacterial arginine repressor. Staphylococcus aureus infection is difficult to eradicate because of biofilm formation and antibiotic resistance. The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection necessitates the development of a new agent against bacterial biofilms. We report a new coumarin compound, termed DCH, that effectively combats MRSA in vitro and in vivo and exhibits potent antibiofilm activity without detectable resistance. Cellular proteome analysis suggests that the molecular mechanism of action of DCH involves the arginine catabolic pathway. Using molecular docking and binding affinity assays of DCH, and comparison of the properties of wild-type and ArgR-deficient MRSA strains, we demonstrate that the arginine repressor ArgR, an essential regulator of the arginine catabolic pathway, is the target of DCH. These findings indicate that DCH is a promising lead compound and validate bacterial ArgR as a potential target in the development of new drugs against MRSA biofilms.