Key Laboratory for Green Chemical Process of Ministry of Education, School of Environmental Ecology and Biological Engineering, Wuhan Institute of Technology, Wuhan, 430205, People's Republic of China.
Int J Nanomedicine. 2021 Nov 19;16:7741-7757. doi: 10.2147/IJN.S333432. eCollection 2021.
As a biofilm-associated disease, dental caries benefits from nanoparticle (NP)-based therapies. () is a primary aetiologic agent for dental caries development. We successfully applied a synergistic therapy of Ag/ZnO nanocomposites combined with light-emitting diode (LED) radiation to inhibit biofilms. However, the antibiofilm mechanism has not been fully elucidated, and little is known about the biofilm formation ability of bacteria that survive NP-based therapies.
This study explored the antibiofilm formation mechanism of this synergistic therapy by an integrated approach based upon proteomics.
Synergistic therapy killed 99.8% of bacteria, while the biofilm formation ability of 0.2% surviving bacteria was inhibited. The proteomic responses of to synergistic therapy were comprehensively characterized to unveil the mechanism of bacterial death and biofilm formation inhibition of the surviving bacteria. In total, 55 differentially expressed proteins (12 upregulated and 43 downregulated) were recorded. The bioinformatic analysis demonstrated that cellular integrity damage and regulated expression of structure-associated proteins were the main reasons for bacterial death. In addition, the proteomic study indicated the potential inhibition of metabolism in surviving bacteria and provided a biofilm-related network consisting of 17 differentially expressed proteins, explaining the multiantibiofilm formation actions. Finally, we reported and verified the inhibitory effects of synergistic therapy on sucrose metabolism and D-alanine metabolism, which disturbed the biofilm formation of surviving bacteria.
Our findings demonstrated that synergistic therapy killed most bacteria and inhibited the surviving bacteria from forming biofilms. Furthermore, the antibiofilm formation mechanism was revealed by proteomics analysis of after synergistic therapy and subsequent metabolic studies. Our success may provide a showcase to explore the antibiofilm formation mechanism of NP-based therapies using proteomic studies.
作为一种生物膜相关疾病，龋齿受益于基于纳米粒子（NP）的治疗。（）是龋齿发展的主要病因。我们成功地应用了银/氧化锌纳米复合材料与发光二极管（LED）辐射相结合的协同治疗来抑制生物膜。然而，其抗生物膜机制尚未完全阐明，对于在基于 NP 的治疗后存活的细菌的生物膜形成能力知之甚少。
本研究通过基于蛋白质组学的综合方法探索了这种协同治疗的抗生物膜形成机制。
协同治疗杀死了 99.8%的细菌，而 0.2%存活细菌的生物膜形成能力受到抑制。全面描绘了（）对协同治疗的蛋白质组反应，以揭示细菌死亡和存活细菌生物膜形成抑制的机制。总共记录了 55 个差异表达蛋白（12 个上调和 43 个下调）。生物信息学分析表明，细胞完整性损伤和结构相关蛋白的调节表达是细菌死亡的主要原因。此外，蛋白质组学研究表明，代谢可能受到抑制，并且提供了一个由 17 个差异表达蛋白组成的与生物膜相关的网络，解释了多抗生物膜形成作用。最后，我们报告并验证了协同治疗对蔗糖代谢和 D-丙氨酸代谢的抑制作用，这扰乱了存活细菌的生物膜形成。
我们的研究结果表明，协同治疗杀死了大多数细菌，并抑制了存活细菌形成生物膜。此外，通过协同治疗后（）的蛋白质组学分析和随后的代谢研究揭示了抗生物膜形成机制。我们的成功可能为使用蛋白质组学研究探索基于 NP 的治疗的抗生物膜形成机制提供了一个范例。
