Department of Clinical & Toxicological Analysis, School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.
Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.
J Med Microbiol. 2023 Sep;72(9). doi: 10.1099/jmm.0.001751.
Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant (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. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress. 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 analysis. The aim of this study was to evaluate the antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml, 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. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of 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.
抗生素耐药性是公共卫生的主要威胁，特别是耐甲氧西林金黄色葡萄球菌（MRSA）是抗菌药物耐药性的主要原因。为了应对这一问题，药物再利用为发现新的抗菌剂提供了一个有前途的解决方案。甲萘醌对甲氧西林敏感和耐甲氧西林的金黄色葡萄球菌菌株均具有单独和与苯唑西林联合使用的抗菌活性。其主要作用机制涉及诱导氧化应激。使用肉汤微量稀释法进行了敏感性测定。使用棋盘技术评估了甲萘醌、苯唑西林和抗氧化剂之间的相互作用。使用流式细胞术、荧光显微镜和分析评估了作用机制。本研究旨在评估甲萘醌对浮游生物和生物膜形式的甲氧西林敏感和耐药金黄色葡萄球菌菌株的抗菌潜力。它还研究了其作为苯唑西林活性调节剂的作用，并研究了其活性涉及的作用机制。甲萘醌对浮游细胞的浓度范围为 2 至 32μg/ml 时表现出抗菌活性，具有抑菌作用。与苯唑西林联合使用时，对测试菌株表现出相加和协同作用。甲萘醌在亚抑菌浓度下也表现出抗生物膜活性，并有效对抗单独使用苯唑西林时敏感性降低的生物膜。其作用机制涉及活性氧（ROS）的产生和 DNA 损伤。它还显示出与重要靶标（如 DNA 回旋酶和去氢表雄甾酮合酶）的相互作用。抗坏血酸的存在逆转了其作用。甲萘醌对耐甲氧西林金黄色葡萄球菌菌株表现出抗菌和抗生物膜活性，表明其作为治疗金黄色葡萄球菌感染的辅助药物的潜力。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得到补充。
