Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran.
Department of Photodynamic, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran.
Arch Microbiol. 2024 Jun 15;206(7):304. doi: 10.1007/s00203-024-04028-x.
The extension of multidrug-resistant strains of Staphylococcus aureus (S. aureus) is one of the main health challenges in the world, which requires serious solutions to deal with it. Combination therapies using conventional antibiotics and new antibacterial compounds that target different bacterial pathways are effective methods against resistant bacterial infections. Gallium is an iron-like metal that competes with iron for uptake into bacteria and has the potential to disrupt iron-dependent vital processes in bacteria. In this study, we explored the antibacterial effects of gallium nitrate (Ga(NO)) and vancomycin alone and in combination with each other on methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) using microdilution assay and checkerboard test, respectively. Then, their effect on the formation and destruction of biofilms was investigated. Finally, the amount of ROS production in the presence of these two compounds in bacteria was evaluated. The results indicated that the vancomycin/ Ga(NO) combination reduced the MIC of vancomycin in the MRSA strain and had an additive effect on it. Vancomycin plus Ga(NO) reduced the formation of biofilms and increased the destruction of biofilms formed in both strains, especially in the MRSA strain. ROS production was also higher in the combination of vancomycin with Ga(NO) compared to vancomycin alone, especially in MRSA. Therefore, our results showed that Ga(NO) enhances the antibacterial activity of vancomycin and this combination therapy can be considered as a new strategy for the treatment of MRSA infections.
耐多药金黄色葡萄球菌（S. aureus）菌株的扩展是世界上主要的健康挑战之一，需要采取严重的解决方案来应对。使用传统抗生素和针对不同细菌途径的新型抗菌化合物的联合疗法是对抗耐药细菌感染的有效方法。镓是一种类似于铁的金属，它与铁竞争进入细菌，并有可能破坏细菌中依赖铁的重要过程。在这项研究中，我们使用微量稀释法和棋盘试验分别研究了单独使用硝酸镓（Ga(NO)）和万古霉素以及它们相互组合对甲氧西林敏感金黄色葡萄球菌（MSSA）和耐甲氧西林金黄色葡萄球菌（MRSA）的抗菌作用。然后，研究了它们对生物膜形成和破坏的影响。最后，评估了这两种化合物在细菌中产生 ROS 的量。结果表明，万古霉素/ Ga(NO)组合降低了 MRSA 菌株中万古霉素的 MIC 值，并对其具有相加作用。万古霉素加 Ga(NO)降低了两种菌株中生物膜的形成，并增加了对生物膜的破坏，尤其是在 MRSA 菌株中。与单独使用万古霉素相比，在万古霉素与 Ga(NO)的组合中，ROS 的产生也更高，尤其是在 MRSA 中。因此，我们的结果表明，Ga(NO)增强了万古霉素的抗菌活性，这种联合治疗可以被视为治疗 MRSA 感染的一种新策略。
