Methicillin-resistant Staphylococcus aureus and the formation of persistent nongrowing subpopulations (persisters) is a serious threat to human. Our previous studies have proved that two cajaninstilbene acid (CSA) analogues, compound 5b and 5j display remarkable antibacterial activities, especially overcoming drug resistance of methicillin-resistant Staphylococcus aureus (MRSA). Present study found that 5b and 5j are capable of eradicating MRSA persisters. However, their underlying antibacterial mechanism is still obscure. In this study, biological evaluation was performed by transmission electron micrograph, membrane permeability and membrane depolarization experiment to reveal the effects of drugs on bacteria. Further, affinity-based protein profiling and transcriptional profiling were performed to characterise the protein targets in bacterial. Biological evaluation suggested that 5b has an effect on bacterial membrane, affinity-based protein profiling identified that 5b targets membrane associated protein PgsA and verified by in vitro labelling profile. Transcriptional profiling indicated that 5b interferes in phosphatidylglycerol (PG) synthesis pathway. This study identified a novel antibacterial target PgsA and it might be a potential target to combat the resistant bacteria.

中文翻译：

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生物学评估和化学蛋白质组学揭示了cajaninstilbene-酸类似物的潜在抗菌靶标。

耐甲氧西林的金黄色葡萄球菌和持续的不增长的亚群（持久性有机污染物）的形成是对人类的严重威胁。我们以前的研究已经证明，两种卡积斯汀二烯酸（CSA）类似物化合物5b和5j显示出显着的抗菌活性，尤其是克服了耐甲氧西林的金黄色葡萄球菌（MRSA）的耐药性。目前的研究发现5b和5j能够消除MRSA持久性。但是，它们潜在的抗菌机制仍然不清楚。在这项研究中，通过透射电子显微照片，膜通透性和膜去极化实验进行了生物学评估，以揭示药物对细菌的作用。此外，进行了基于亲和力的蛋白质谱和转录谱分析，以表征细菌中的蛋白质靶标。生物学评估表明5b对细菌膜有影响，基于亲和力的蛋白质谱分析确定5b靶向膜相关蛋白PgsA，并通过体外标记进行验证。转录谱分析表明5b干扰磷脂酰甘油（PG）的合成途径。这项研究确定了一种新型的抗菌靶标PgsA，它可能是对抗耐药菌的潜在靶标。