Department of Microbiology, Savitribai Phule Pune University, Pune, 411007, Maharashtra, India.
Curr Microbiol. 2022 Aug 8;79(9):282. doi: 10.1007/s00284-022-02975-6.
Menadione is an analogue of 1,4-naphthoquinone (1,4-NQ) that possesses enormous pharmaceutical potential. The minimum inhibitory concentration (MIC) of menadione was determined against eighteen pathogens of the ESKAPE category, including thirteen multidrug-resistant (MDR) and five standard strains. From a total of eighteen pathogens, five strains of S. aureus (four: MDR and one: Standard strain) were considered further for detailed studies. This study included the determination of minimum bactericidal concentration (MBC), time-kill assay, scanning electron microscopic technique (SEM), and detection of reactive oxygen species (ROS). Additionally, the effect of menadione on biofilms of three strains of S. aureus was performed through crystal violet assay, SEM, and confocal laser scanning microscopy (CLSM). Menadione exerted substantial antibacterial activity against S. aureus (S8, S9, NCIM 5021) at a lower MIC (64 µg/mL). Whereas, the MIC of 256 µg/mL was displayed against J2 and J4 (MDR and biofilm-forming strains). The time-killing effect of menadione against S. aureus strains was observed after 9 h at MBCs of 64 µg/mL (NCIM 5021), 128 µg/mL (S8, S9), and 512 µg/mL (J2, J4). Enhanced levels of ROS in all five S. aureus were observed in presence of menadione (MICs and MBCs). The relation of enhanced ROS due to menadione activity invigorated us to explore its effect on S. aureus biofilms. We report menadione-mediated inhibition (> 90%) of biofilm formation (at respective MICs) and effect on preformed biofilms (> 85%) at 1024 µg/mL. Menadione possessing antibacterial and antibiofilm potentials are imperative in the era of multidrug resistance developed by bacterial pathogens.
亚甲二氢醌是 1,4-萘醌（1,4-NQ）的类似物，具有巨大的药物潜力。亚甲二氢醌对 ESKAPE 类别的 18 种病原体的最小抑菌浓度（MIC）进行了测定，其中包括 13 种多药耐药（MDR）和 5 种标准株。在总共 18 种病原体中，进一步对 5 株金黄色葡萄球菌（4 株：MDR 和 1 株：标准株）进行了详细研究。本研究包括最小杀菌浓度（MBC）的测定、时间杀伤试验、扫描电子显微镜技术（SEM）和活性氧（ROS）的检测。此外，通过结晶紫试验、SEM 和共聚焦激光扫描显微镜（CLSM）对三种金黄色葡萄球菌生物膜的亚甲二氢醌作用进行了研究。亚甲二氢醌对金黄色葡萄球菌（S8、S9、NCIM 5021）的抗菌活性较强，MIC 较低（64µg/mL）。然而，J2 和 J4（MDR 和生物膜形成株）的 MIC 为 256µg/mL。亚甲二氢醌对金黄色葡萄球菌菌株的时间杀伤作用在 MBC 为 64µg/mL（NCIM 5021）、128µg/mL（S8、S9）和 512µg/mL（J2、J4）时观察到 9 小时后。在亚甲二氢醌（MIC 和 MBC）存在下，所有 5 株金黄色葡萄球菌的 ROS 水平均升高。由于亚甲二氢醌活性导致 ROS 水平升高，我们进一步研究了其对金黄色葡萄球菌生物膜的影响。我们报告了亚甲二氢醌介导的抑制（分别在各自的 MIC 下）>90%的生物膜形成和在 1024µg/mL 时对预先形成的生物膜的影响>85%。在细菌病原体产生的多药耐药时代，具有抗菌和抗生物膜潜力的亚甲二氢醌是至关重要的。
