权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Antimicrobial mechanisms of action zinc oxide nanoparticles

氧化锌纳米粒子的抗菌作用机制

基本信息

批准号：
9918245
负责人：
J SCOTT VANEPPS
金额：
$ 19.44万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-23 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9918245
关键词：
Address Adhesions Affect Anti-Bacterial Agents Antibiotic Therapy Antibiotics Appointment Bacteria Behavior Binding Biocompatible Materials Biomimetics Cell Death Cell Respiration Cell Wall Cell physiology Cells Cessation of life Chemistry Clinical Clinical Medicine Complex Data Development Development Plans Device Designs Devices Educational workshop Engineering Enzyme Inhibition Enzyme Inhibitor Drugs Enzymes Evaluation Funding Generations Genes Genomics Goals Grant Growth Immune response Implant Infection Infection prevention Lead Libraries Life Liquid Chromatography Literature Mammalian Cell Mass Spectrum Analysis Mediating Medical Device Medicine Membrane Mentored Clinical Scientist Development Award (K08)Mentors Mentorship Metabolic Pathway Michigan Microbial Biofilms Microbiology Modification Molecular Biology NP protein Operating Rooms Operative Surgical Procedures Oxidative Stress Pathogenicity Patients Predisposition Preparation Process Property Proteins Proteomics Publications Reactive Oxygen Species Research Resources Scientist Secure Sepsis Shapes Staphylococcus aureus Surface System Techniques Technology Testing Therapeutic Time Training Translational Research Universities Work Zinc Oxide antimicrobial antimicrobial peptide biological adaptation to stress career career development cohort college combat commercialization cost estimate didactic education experience extracellular gel electrophoresis graduate student healthcare-associated infections implant material implantable device in vivo infection rate innovation interest materials science medical implant meetings microbial multidisciplinary mutant nanomaterials nanoparticle new technology novel pathogen preservation prevent product development programs protein complex research and development symposium

项目摘要

PROJECT SUMMARY: Despite a decade of engineering advancements and clinical process improvements, 1 million healthcare- associated infections in the U.S. can be attributed to indwelling medical devices annually. Zinc oxide nanoparticles (ZnO-NPs) are one of the most promising emerging antimicrobials with potential to combat device related infection. ZnO-NPs are inexpensive, stable, and easy to prepare with broad antimicrobial spectrum and wide therapeutic window. However, the antimicrobial mechanism of action of ZnO-NPs remains elusive. This proposal is specifically motivated to better understand the mechanism of action of ZnO-NPs. Such understanding is necessary to guide the design of device coatings that preserve antibacterial function in vivo. Reactive oxygen species (ROS) generation or membrane disruption are hypothesized mechanisms of action. However the literature is inconsistent and our preliminary data suggests that these NP effects are not sufficient. We recently demonstrated that ZnO-NPs have shape-dependent, biomimetic, reversible, enzyme inhibition properties. The central research question for this career development grant is: To what extent does ZnO-NP behavior as an enzyme inhibitor contribute to antimicrobial activity? I have multidisciplinary training in medicine, engineering, and molecular biology that is well-suited to address this question. My ultimate career goal is to become a clinician-scientist. I plan to have a clinical interest in sepsis as it relates to indwelling medical devices and an independently funded research program focused on the development of novel biomaterials to resist microbial contamination and infection. This proposal was developed to solidify my expertise, formalize my research niche, and garner the resources for the next phase of career development. My specific career development objectives for the next four years are to: 1. Solidify my expertise in microbiology (including biofilm microbiology), microbial-surface interaction, nanoparticle technology, and translational research. 2. Master techniques in evaluating mechanisms of action of antimicrobial and anti-biofilm materials. 3. Generate sufficient preliminary data and publication record to obtain independent research funding. 4. Secure my niche as an expert in bacterial-nanomaterial interactions. 5. Obtain secondary appointment in the College of Engineering so that I can work with and mentor graduate students in their research and career development. I have assembled a mentorship team of experts co-localized at the University of Michigan North Campus Research Complex with experience in clinical medicine, microbiology, material science and engineering, and product development/commercialization. Together we have devised a highly-individualized, project-oriented training plan that includes regular mentorship meetings, formal didactic education, career development workshops, and presentation at local and national conferences. Partnered with this career development plan is an innovative research plan. By synthesizing ZnO-NPs that are identical in surface chemistry but differ only in shape we can control the potential for enzyme inhibition and address the central research question above. Using these novel preparations, we will test the hypothesis: Pyramidal ZnO-NPs inhibit a cohort of bacterial enzymes which are critical to survival. Our research specific aims are to: 1. Quantify aerobic metabolism, membrane integrity, and microbial death in a commonly isolated medical device pathogen (i.e., Staphylococcus aureus) as a function of exposure time to spherical vs pyramidal ZnO-NPs. 2. Identify genes involved in enzyme inhibition by ZnO-NPs using a mariner transposon mutant library of S. aureus. 3. Determine the subset of S. aureus proteins that specifically complex with ZnO-NPs in a shape- dependent manner by 2D-gel electrophoresis followed by liquid chromatography paired with tandem mass spectroscopy (LC-MS/MS).

项目总结: