Abstract：
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(NO3)3) 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(NO3)3 combination reduced the MIC of vancomycin in the MRSA strain and had an additive effect on it. Vancomycin plus Ga(NO3)3 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(NO3)3 compared to vancomycin alone, especially in MRSA. Therefore, our results showed that Ga(NO3)3 enhances the antibacterial activity of vancomycin and this combination therapy can be considered as a new strategy for the treatment of MRSA infections.
摘要：
金黄色葡萄球菌(S.金黄色葡萄球菌）是世界上主要的健康挑战之一，这需要严肃的解决方案来处理它。使用常规抗生素和靶向不同细菌途径的新抗菌化合物的组合疗法是对抗抗性细菌感染的有效方法。镓是一种类似铁的金属，与铁竞争吸收到细菌中，并有可能破坏细菌中依赖铁的重要过程。在这项研究中,我们探讨了硝酸镓（Ga（NO3）3）和万古霉素单独和联合使用对甲氧西林敏感的金黄色葡萄球菌（MSSA）和耐甲氧西林金黄色葡萄球菌（MRSA）的抗菌作用，使用微量稀释试验和棋盘测试，分别。然后，研究了它们对生物膜形成和破坏的影响。最后,评估了在细菌中存在这两种化合物的情况下ROS产生的量。结果表明，万古霉素/Ga（NO3）3组合降低了万古霉素在MRSA菌株中的MIC，并对其具有累加作用。万古霉素加Ga（NO3）3减少了生物膜的形成，并增加了在两个菌株中形成的生物膜的破坏，尤其是MRSA菌株。与单独的万古霉素相比，万古霉素与Ga（NO3）3的组合中的ROS产生也更高。尤其是MRSA。因此,我们的结果表明,Ga(NO3)3增强了万古霉素的抗菌活性,这种联合治疗可被视为MRSA感染治疗的新策略.
