甲萘醌
微生物学
金黄色葡萄球菌
抗菌活性
抗菌剂
生物膜
抗菌剂
抗生素
DNA旋转酶
肉汤微量稀释
生物
化学
最小抑制浓度
细菌
生物化学
大肠杆菌
氧化应激
基因
遗传学
作者
Amanda Cavalcante Leitão,Thais Lima Ferreira,Lívia Gurgel do Amaral Valente Sá,Daniel Sampaio Rodrigues,Beatriz Oliveira de Souza,Amanda Dias Barbosa,Lara Elloyse Almeida Moreira,João Batista de Andrade Neto,Vitória Pessoa de Farias Cabral,Maria Erivanda França Rios,Bruno Coêlho Cavalcanti,Jacilene Silva,Emmanuel Silva Marinho,Hélcio Silva dos Santos,Manoel Odorico de Moraes,Hélio Vitoriano Nobre Júnior,Cecília Rocha da Silva
摘要
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.
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