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<i>Staphylococcus aureus</i> （<i>S. aureus</i>）, more specifically methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), is a bacterial pathogen that poses a serious threat to human health. MRSA exhibits a high degree of resistance and multiple virulence factors, especially the formation of biofilm that increasingly complicate treatment. Therefore, it is essential to develop novel antimicrobials. Here we investigated artesunate (ART), a sesquiterpene lactone extracted from Artemisia annua, as an antivirulence agent and antimicrobial sensitizer of <i>S. aureus</i>. In this study, it was showed that ART significantly reduced biofilm formation by <i>S. aureus</i> at sub-minimal inhibitory concentrations (MICs) through the inhibition of polysaccharide intercellular adhesin (PIA) production, without affecting bacterial growth. Molecular docking indicated that the down-regulated <i>icaA</i> gene identified in qRT-PCR may be the target of ART. Moreover, evidence was brought that ART reduced hemolysin, lipase, and nuclease activities and attenuated <i>S. aureus</i> infections in <i>Galleria mellonella</i> models. Notably, checkerboard assays showed that the combination of ART with erythromycin, gentamicin, and vancomycin can exert synergistic effects on <i>S. aureus</i>. Low concentrations of ART were sufficient to sensitize erythromycin-resistant strains of <i>S. aureus</i>, such as the Newman strain. This study highlighted the antibiofilm and antivirulence potential of ART against <i>S. aureus</i>, and brought evidence that it may act as an antimicrobial sensitizer to avoid the development of multidrug-resistant bacteria. In conclusion, ART is a safe and effective antibiotic adjuvant against <i>S. aureus</i> infection.

<i>金黄色葡萄球菌（Staphylococcus aureus）</i>，特指耐甲氧西林金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus, MRSA），是一类严重威胁人类健康的细菌性病原菌。MRSA兼具高度耐药性与多种毒力因子，其所形成的生物被膜进一步加剧了临床治疗的难度。因此，研发新型抗菌药物迫在眉睫。
本研究选取从黄花蒿（Artemisia annua）中提取的倍半萜内酯类化合物青蒿琥酯（artesunate, ART）为研究对象，探究其作为金黄色葡萄球菌抗毒力剂与抗菌增敏剂的应用价值。
研究结果显示，在亚最低抑菌浓度（sub-minimal inhibitory concentrations, MICs）下，ART可通过抑制多糖细胞间粘附素（polysaccharide intercellular adhesin, PIA）的合成，显著削弱金黄色葡萄球菌的生物被膜形成能力，且不影响细菌的正常生长增殖。分子对接实验表明，通过实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction, qRT-PCR）检测到的表达下调的icaA基因，可能是ART的作用靶点。
此外，实验证实ART可降低溶血素、脂肪酶与核酸酶的活性，并在大蜡螟（Galleria mellonella）感染模型中减弱金黄色葡萄球菌的致病力。值得注意的是，棋盘格药敏实验（checkerboard assays）结果显示，ART分别与红霉素、庆大霉素、万古霉素联用时，对金黄色葡萄球菌均可产生协同抗菌效应。低浓度的ART即可有效敏化耐红霉素的金黄色葡萄球菌菌株，如新曼菌株（Newman strain）。
本研究明确了ART抗金黄色葡萄球菌生物被膜与毒力的潜在活性，并证明其可作为抗菌增敏剂，有助于延缓多重耐药菌的演化。综上，ART是一种安全有效的抗生素佐剂，可用于对抗金黄色葡萄球菌感染。