Abstract：
Introduction. Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant Staphylococcus aureus (MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial agents.Hypothesis. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant S. aureus strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress.Methodology. Sensitivity assays were performed using broth microdilution. The interaction between menadione, oxacillin, and antioxidants was assessed using checkerboard technique. Mechanism of action was evaluated using flow cytometry, fluorescence microscopy, and in silico analysis.Aim. The aim of this study was to evaluate the in vitro antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant S. aureus strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity.Results. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml-1, with bacteriostatic action. When combined with oxacillin, it exhibited an additive and synergistic effect against the tested strains. Menadione also demonstrated antibiofilm activity at subinhibitory concentrations and effectively combated biofilms with reduced sensitivity to oxacillin alone. Its mechanism of action involves the production of reactive oxygen species (ROS) and DNA damage. It also showed interactions with important targets, such as DNA gyrase and dehydroesqualene synthase. The presence of ascorbic acid reversed its effects.Conclusion. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of S. aureus infections. The main mechanism of action involves the production of ROS, which subsequently leads to DNA damage. Additionally, the activity of menadione can be complemented by its interaction with important virulence targets.
摘要：
Introduction.抗生素耐药性是对公众健康的主要威胁，特别是耐甲氧西林金黄色葡萄球菌（MRSA）是抗生素耐药性的主要原因。为了解决这个问题，药物再利用为发现新的抗菌剂提供了一个有希望的解决方案。假说。Menadione对甲氧西林敏感和耐甲氧西林金黄色葡萄球菌菌株具有抗菌活性，单独和与苯唑西林联合使用。其主要作用机制涉及诱导氧化应激。方法论。使用肉汤微量稀释进行灵敏度测定。甲萘醌之间的相互作用，苯唑西林,抗氧化剂使用棋盘技术进行评估。使用流式细胞术评估作用机制，荧光显微镜,和硅分析。瞄准.这项研究的目的是评估甲萘醌对甲氧西林敏感和耐药金黄色葡萄球菌菌株的浮游和生物膜形式的体外抗菌潜力。它还研究了其作为苯唑西林活性调节剂的作用，并研究了其活性所涉及的作用机制。结果。Menadione在2至32µgml-1的浓度范围内对浮游细胞具有抗菌活性，具有抑菌作用。当与苯唑西林合用时，它对测试菌株表现出累加和协同作用。甲萘醌还在亚抑制浓度下表现出抗生物膜活性，并有效对抗生物膜，对单独苯唑西林的敏感性降低。其作用机制涉及活性氧（ROS）的产生和DNA损伤。它还显示了与重要目标的相互作用，如DNA促旋酶和脱氢埃角鲨烯合酶。抗坏血酸的存在逆转了其作用。结论。甲萘醌对MRSA菌株具有抗菌和抗生物膜活性，提示其作为治疗金黄色葡萄球菌感染的辅助手段的潜力。主要作用机制涉及ROS的产生，随后导致DNA损伤。此外,甲萘醌的活性可以通过与重要毒力靶标的相互作用来补充。
