Understanding the antimicrobial mechanism of metal nanoparticles using super resolution fluorescence microscopy

使用超分辨率荧光显微镜了解金属纳米颗粒的抗菌机制

• 批准号: 1826642
• 负责人: Yong Wang
• 金额: $ 49.9万
• 依托单位: University of Arkansas
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1826642&HistoricalAwards=false
• 关键词: Understanding; antimicrobial; mechanism; metal; nanoparticles

Antibiotic resistance of bacteria has become one of the biggest threats to public health in the United States and all over the world. Among the alternative antimicrobial agents, metal nanoparticles have attracted broad interests and attention due to their capabilities for suppressing the growth of bacteria and killing bacteria. However, the exact mechanisms for the antimicrobial effects of metal nanoparticles remain poorly understood. This project will establish the fundamental mechanisms of the antimicrobial behavior of metal nanoparticles as alternatives to commonly prescribed antibiotics. The research team will develop and use advanced imaging tools and techniques with superior spatial and temporal resolution to investigate the interactions between individual live bacteria and silver nanoparticles and obtain knowledge of silver nanoparticles' antimicrobial effects. Results from this research will provide guiding principles on the design and production of metal nanoparticles for antimicrobial applications in food safety and hospital infection-treatments, thus improving U.S. public health and benefiting society. Furthermore, comprehensive education and outreach activities will be implemented to cultivate the interests of America's next generation of scientists and engineers, and provide them with experience in and knowledge of nanomaterials and their applications. This will reinforce and improve the United States' future competitive strengths in STEM fields.The goal of this research is to obtain a quantitative understanding of the antimicrobial mechanism of silver nanoparticles and their interactions with live bacteria at the single-cell level. This will be accomplished by developing methodologies using super-resolution fluorescence microscopy, which will allow the studies of individual biomolecules (e.g., proteins, DNA, and lipids) and their dynamics with a spatial resolution of 20 nanometers and a temporal resolution of 10-30 milliseconds. The goal of the research will be achieved by (1) identifying the effects of silver nanoparticles on spatial organization and function of nucleoid-associated proteins; (2) quantifying how bacterial membrane is damaged by silver nanoparticles; and (3) measuring the dependence of silver nanoparticles? effectiveness on particle shapes, charges, and surface modifications. The results from super-resolution fluorescence microscopy will be validated and complemented by conventional biological techniques and assays. This research will address the current existing controversies surrounding the antimicrobial mechanisms of metal nanoparticles, which are due in part to the lack of both temporal and spatial resolution on single live bacteria. The result will be a better understanding of the nano-bio interface at the cellular and molecular levels. This research will provide valuable, quantitative information necessary to guide the rational design and fabrication of metal nanoparticles for antimicrobial applications. The methodologies developed in this research are expected to be applicable to other nanostructures and different types of bacteria.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

细菌的抗生素耐药性已成为美国和世界各地对公共卫生的最大威胁之一。在替代性抗菌剂中，金属纳米颗粒由于抑制细菌生长和杀死细菌的能力而引起了广泛的兴趣和关注。然而，金属纳米颗粒的抗菌作用的确切机制仍然鲜为人知。该项目将建立金属纳米颗粒抗菌行为的基本机制，作为普遍处方抗生素的替代方法。研究团队将开发和使用具有优越的空间和时间分辨率的先进成像工具和技术，以研究单个活细菌与银纳米颗粒之间的相互作用，并获得银纳米颗粒抗菌作用的知识。这项研究的结果将提供有关金属纳米颗粒的设计和生产的指导原则，用于食品安全和医院感染治疗中的抗菌应用，从而改善了美国的公共卫生和受益社会。此外，将实施全面的教育和外展活动，以培养美国下一代科学家和工程师的利益，并为他们提供纳米材料及其应用方面的经验和知识。这将加强和改善美国在STEM领域的未来竞争优势。这项研究的目的是对银纳米颗粒的抗菌机制进行定量了解及其与单细胞水平上的活细菌的相互作用。这将通过使用超分辨率荧光显微镜开发方法来实现，这将允许研究单个生物分子（例如蛋白质，DNA和脂质）及其动力学，并具有20纳米量的空间分辨率和10-30毫秒的时间分辨率。 （1）确定银纳米颗粒对核苷相关蛋白的空间组织和功能的影响，将实现研究的目的； （2）量化细菌膜如何受到银纳米颗粒的破坏； （3）测量银纳米颗粒的依赖性？对粒子形状，电荷和表面修饰的有效性。超分辨率荧光显微镜的结果将得到传统的生物技术和测定的验证和补充。这项研究将解决围绕金属纳米颗粒抗菌机制的当前争议，这部分是由于缺乏单个活细菌的时间和空间分辨率。结果将更好地理解细胞和分子水平的纳米生物界面。这项研究将提供必要的有价值的定量信息，以指导金属纳米颗粒的合理设计和制造用于抗微生物应用。预计这项研究中开发的方法将适用于其他纳米结构和不同类型的细菌。该奖项反映了NSF的法定任务，并且使用基金会的智力优点和更广泛的审查标准，被认为值得通过评估来提供支持。

项目成果

Silver Ions Caused Faster Diffusive Dynamics of Histone-Like Nucleoid-Structuring Proteins in Live Bacteria

• DOI: 10.1128/aem.02479-19
• 发表时间: 2020-03-01
• 期刊: APPLIED AND ENVIRONMENTAL MICROBIOLOGY
• 影响因子: 4.4
• 作者: Sadoon, Asmaa A.;Khadka, Prabhat;Wang, Yong
• 通讯作者: Wang, Yong

Stability of Polyethylene Glycol-Coated Copper Nanoparticles and Their Optical Properties

聚乙二醇包覆铜纳米粒子的稳定性及其光学性能

• DOI: 10.3390/coatings12060776
• 发表时间: 2022
• 期刊: Coatings
• 影响因子: 3.4
• 作者: Okyere, Deborah;Manso, Ryan H.;Tong, Xiao;Chen, Jingyi
• 通讯作者: Chen, Jingyi

Anomalous, non-Gaussian, viscoelastic, and age-dependent dynamics of histonelike nucleoid-structuring proteins in live Escherichia coli

• DOI: 10.1103/physreve.98.042411
• 发表时间: 2018-10
• 期刊: Physical Review E
• 影响因子: 2.4
• 作者: Yong Wang;Asmaa A. Sadoon

Polydopamine Surface Coating Synergizes the Antimicrobial Activity of Silver Nanoparticles

• DOI: 10.1021/acsami.0c10517
• 发表时间: 2020-09-09
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Niyonshuti, Isabelle I.;Krishnamurthi, Venkata Rao;Chen, Jingyi
• 通讯作者: Chen, Jingyi

Microampere Electric Current Causes Bacterial Membrane Damage and Two-Way Leakage in a Short Period of Time

• DOI: 10.1128/aem.01015-20
• 发表时间: 2020-08-01
• 期刊: APPLIED AND ENVIRONMENTAL MICROBIOLOGY
• 影响因子: 4.4
• 作者: Krishnamurthi, Venkata Rao;Rogers, Ariel;Wang, Yong
• 通讯作者: Wang, Yong