由于抗生素的不加区分使用，甲氧西林耐药金黄色葡萄球菌（MRSA）的患病率急剧增加。在这项研究中，我们重新利用赫斯特醇（HXS）作为一种抗菌剂，以抗击浮游和生物膜相关的MRSA感染。HXS是一种非类固醇合成雌激素，靶向雌激素受体（ERα和ERβ），已被用作激素抗肿瘤剂。在我们的工作中，利用MSSA和MRSA菌株的抗菌敏感性确定了最小抑菌浓度（MIC）。利用生物膜抑制和根除试验评估生物膜相关的抗菌活性。利用RTqPCR分析S. aureus的去抗生素作用进行生物膜相关基因的分析。使用棋盘稀释法测试HXS以识别可能具有协同作用的抗生素。测量ATP并检测ATP酶可确定细菌能量代谢。结果显示，HXS表现出有效的抗菌活性，包括两种类型的菌株和临床分离物，MIC为16 μg / mL。亚HXS强烈抑制了S. aureus的粘附。HXS处理后，胞外多聚物质（EPS）含量和eno，sacC，clfA，pls和fnbpB的相对转录水平降低。HXS对S. aureus表现出抗菌效果，并与氨基糖苷有协同作用，通过直接干扰细胞能量代谢来实现。 HXS通过减少相关基因表达抑制粘附和生物膜形成，并根除由MRSA形成的生物膜。此外，HXS增加了氨基糖苷对MRSA的敏感性。总之，HXS是一种重新利用的药物，可能是MRSA感染的一种有前途的治疗选择。 Copyright © 2023 The Authors。 Elsevier GmbH 发布。保留所有权利。

There has been an explosion in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) because of the indiscriminate use of antibiotics. In this study, we repurposed hexestrol (HXS) as an antibacterial agent to fight planktonic and biofilm-related MRSA infections. HXS is a nonsteroidal synthetic estrogen that targets estrogen receptors (ERα and ERβ) and has been used as a hormonal antineoplastic agent. In our work, the minimum inhibitory concentrations (MICs) were determined using the antimicrobial susceptibility of MSSA and MRSA strains. Anti-biofilm activity was evaluated using biofilm inhibition and eradication assays. Biofilm-related genes were analyzed with or without HXS treatment using RTqPCR analysis of S. aureus. HXS was tested using the checkerboard dilution assay to identify antibiotics that may have synergistic effects. Measurement of ATP and detection of ATPase allowed the determination of bacterial energy metabolism. As shown in the results, HXS showed effective antimicrobial activity against S. aureus, including both type strains and clinical isolations, with MICs of 16 µg/mL. Sub-HXS strongly inhibited the adhesion of S. aureus. The content of extracellular polymeric substances (EPS) and the relative transcription levels of eno, sacC, clfA, pls and fnbpB were reduced after HXS treatment. HXS showed antibacterial effects against S. aureus and synergistic activity with aminoglycosides by directly interfering with cellular energy metabolism. HXS inhibits adhesion and biofilm formation and eradicates biofilms formed by MRSA by reducing the expression of related genes. Furthermore, HXS increases the susceptibility of aminoglycosides against MRSA. In conclusion, HXS is a repurposed drug that may be a promising therapeutic option for MRSA infection.Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.