Staphylococcus aureus (S. aureus), especially methicillin-resistant Staphylococcus aureus (MRSA), is a major cause of pneumonia, resulting in severe morbidity and mortality in adults and children. Sortase A (SrtA), which mediates the anchoring of cell surface proteins in the cell wall, is an important virulence factor of S. aureus. Here, we found that salvianolic acid A (Sal A), which is a natural product that does not affect the growth of S. aureus, could inhibit SrtA activity (IC50 = 5.75 μg/ml) and repress the adhesion of bacteria to fibrinogen, the anchoring of protein A to cell wall, the biofilm formation, and the ability of S. aureus to invade A549 cells. Furthermore, in vivo studies demonstrated that Sal A treatment reduced inflammation and protected mice against lethal pneumonia caused by MRSA. More significantly, full protection (a survival rate of 100%) was achieved when Sal A was administered in combination with latamoxef. Together, these results indicate that Sal A could be developed into a promising therapeutic drug to combat MRSA infections while limiting resistance development.

中文翻译：

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丹酚酸A与拉莫昔夫的组合可完全保护小鼠免受由耐甲氧西林的金黄色葡萄球菌引起的致命性肺炎。

金黄色葡萄球菌（S. aureus），特别是耐甲氧西林的金黄色葡萄球菌（MRSA），是引起肺炎的主要原因，导致成年人和儿童的严重发病和死亡。介导细胞表面蛋白在细胞壁中锚定的分选酶A（SrtA）是金黄色葡萄球菌的重要毒力因子。在这里，我们发现丹酚酸A（Sal A）是一种不影响金黄色葡萄球菌生长的天然产物，可以抑制SrtA活性（IC50 = 5.75μg/ ml）并抑制细菌与纤维蛋白原的粘附，蛋白A在细胞壁上的锚定，生物膜形成以及金黄色葡萄球菌侵袭A549细胞的能力。此外，体内研究表明，Sal A治疗可减轻炎症并保护小鼠免受MRSA致死的肺炎。更重要的是 当Sal A与Latamoxef并用时，可达到完全保护（存活率100％）。总之，这些结果表明，Sal A可以发展成为一种有前途的治疗药物，以对抗MRSA感染，同时限制耐药性的发展。