A new coumarin compound DCH combats methicillin-resistant <i>Staphylococcus aureus</i> biofilm by targeting arginine repressor
Di Qu, Zheng Hou, Jing Li, Liyang Luo, Shan Su, Zichen Ye, Yinlan Bai, Xinlei Zhang, Guanghui Chen, Zhoupeng Li, Yikun Wang, Xiaoyan Xue, Xiaoxing Luo, Mingkai Li
Abstract
(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.