Department of Chemical Engineering and Material Science, College of Engineering, Michigan State University, East Lansing, MI 48824, USA.
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
Acta Biomater. 2019 Sep 15;96:537-546. doi: 10.1016/j.actbio.2019.07.012. Epub 2019 Jul 11.
This work describes a novel strategy to combat methicillin-resistant Staphylococcus aureus (MRSA) via the reactivation of inert antibiotics. This strategy exploits a multifunctional system consisting of bioactive glass-ceramic microparticles with antibacterial properties combined with various antibiotics to kill MRSA. Specifically, sol-gel derived silver-doped bioactive glass-ceramic microparticles (Ag-BG) combined with antibiotics that MRSA resists such as oxacillin or fosfomycin, significantly decreased the viability of MRSA. Ag-BG also potentiated the activity of vancomycin on static bacteria, which are typically resistant to this antibiotic. Notably, the synergistic activity is restricted to cell-envelope acting antibiotics as Ag-BG supplementation did not increase the efficacy of gentamicin. Bacteria viability assays and electron microscopy images demonstrate that Ag-BG synergizes to restore antibacterial activity to antibiotics that MRSA resists. The low cytotoxicity previously studied against oral bacteria, together with the known regenerative properties presented in previous studies, and the unique antibacterial properties observed in this work when they are combined with antibiotics, make this multifunctional system a promising approach for healing infected tissue. STATEMENT OF SIGNIFICANCE: This study addresses a very significant issue in the field of antibiotic resistance presenting an innovative way to clear MRSA, by utilizing bioactive glass-ceramic microparticles in combination with antibiotics. Multifunctional glass-ceramic microparticles doped with silver ions (Ag-BG) have been previously observed to exhibit bioactive and antibacterial properties. In this study Ag-BG microparticles were observed to synergize with antibiotics restoring their sensitivity against MRSA. This research work presents a novel approach to resurrect ineffective antibiotics and render them effective against MRSA. Cytotoxicity to eukaryotic cells is not anticipated, as it has been previously observed that these microparticles can trigger hard and soft dental tissue regeneration, when they are utilized in certain concentrations. This study opens a new avenue in the treatment of multidrug resistance bacteria.
这项工作描述了一种通过重新激活惰性抗生素来对抗耐甲氧西林金黄色葡萄球菌（MRSA）的新策略。该策略利用了一种多功能系统，该系统由具有抗菌性能的生物活性玻璃陶瓷微球与各种抗生素结合使用来杀死 MRSA。具体来说，溶胶-凝胶衍生的载银生物活性玻璃陶瓷微球（Ag-BG）与 MRSA 耐药的抗生素（如苯唑西林或磷霉素）结合使用，显著降低了 MRSA 的活力。Ag-BG 还增强了万古霉素对静态细菌的活性，而这些细菌通常对这种抗生素具有耐药性。值得注意的是，协同作用仅限于作用于细胞包膜的抗生素，因为 Ag-BG 的补充并没有增加庆大霉素的疗效。细菌活力测定和电子显微镜图像表明，Ag-BG 协同作用恢复了抗生素对 MRSA 的耐药性。之前对口腔细菌的研究已经表明其低细胞毒性，加上之前的研究中已经证明的再生特性，以及当它们与抗生素结合时在这项工作中观察到的独特的抗菌特性，使得这种多功能系统成为一种有前途的方法来治愈感染组织。意义声明：本研究解决了抗生素耐药领域的一个非常重要的问题，提出了一种利用生物活性玻璃陶瓷微球与抗生素联合清除 MRSA 的创新方法。之前已经观察到掺杂银离子的多功能玻璃陶瓷微球（Ag-BG）具有生物活性和抗菌性能。在这项研究中，Ag-BG 微球被观察到与抗生素协同作用，恢复了它们对 MRSA 的敏感性。这项研究工作提出了一种使无效抗生素复活并使其对 MRSA 有效的新方法。由于之前已经观察到这些微球在一定浓度下可以触发硬组织和软组织再生，因此预计对真核细胞的细胞毒性不会产生影响。这项研究为治疗多药耐药菌开辟了新途径。
