Mechanics-Targeting Strategies for Biofilm Prevention and Remediation

生物膜预防和修复的力学目标策略

• 批准号: 1727544
• 负责人: Vernita Gordon
• 金额: $ 37.08万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1727544&HistoricalAwards=false
• 关键词: Mechanics; Targeting; Strategies; Biofilm; Prevention

Biofilms are communities of microbes that are bound to each other by a matrix of polymers and proteins that they produce in which to live. Biofilms foul and corrode pipes, and partially cause chronic infections in animals and humans. The biofilm "hides" the bacteria from many antibiotics and bacteriocides, and also masks them from the immune system. This project is to determine the role of shear mechanics in the creating the biofilms made by an important pathogen that affects humans. This will benefit society by laying the groundwork for new approaches to preventing and clearing biofilms that target mechanical characteristics. Today the approaches to preventing biofilms focus, with limited success, on developing surfaces that resist bacterial attachment or that kill bacteria. Mature biofilms often resist treatment, except by mechanical removal, and mechanical breakup of biofilms can also increase vulnerability to conventional antibiotics. Almost nothing is known about how different matrix materials control the mechanics of biofilms. This research will improve biofilm prevention and remediation and benefit public health and infrastructure where biofilms are a problem such as in the piping of water treatment plants, and oil transport piping. Educational modules to be developed in the first Educational goal will be aligned with standards for high school curricula in biology, physics, and math, provide an experiential understanding of how scientific knowledge is developed and teach discipline-crossing core concepts. The second educational goal will lead to better strategies for improving the long-term undergraduate STEM pipeline for both traditional and under-represented groups.Pseudomonas aeruginosa is a model organism with well-characterized genetics and molecular biology, and also readily forms biofilms with important industrial and medical impact. Biofilm mechanics will be measured using rheology. Controlled stress will be applied to single bacteria and to bacteria within biofilms, and the resulting signaling, phenotypic changes, and biofilm development will be measured. Genetic manipulation will be used to elucidate how specific gene products contribute to specific mechanical properties and to mechanosensing, signaling, and biofilm initiation. Research Aims are: (1) determine the role of shear mechanics in triggering the signal that initiates biofilm development - this will reveal design principles for surfaces that thwart mechanosensing and thereby prevent biofilm initiation; (2) determine the role of specific biofilm components in contributing to mechanical resilience of the mature biofilm - this will result in strategies for disruption and clearance that are tunable to specific matrix composition and mechanical properties; (3) determine the mechanosensory response of constituent bacteria to biofilm stiffness and strain - this will indicate how to reduce biofilms' ability to dynamically adapt and increase their mechanical robustness. (1) Research Aim 1 will result in a new paradigm for biofilm prevention that targets highly-conserved signaling mechanisms for which evolutionary escape will be difficult or impossible. (2) Research Aim 2 will result in a new framework for understanding the mechanics of biofilms as composites. (3) Research Aim 3 will result in new knowledge of how biofilms may act as multicellular, force sensitive "tissues".

生物膜是微生物的群落，它们通过它们产生的聚合物和蛋白质基质彼此结合在一起。生物膜污染和腐蚀管道，并部分导致动物和人类的慢性感染。 生物膜“隐藏”细菌免受许多抗生素和杀菌剂的侵害，也使它们免受免疫系统的侵害。本项目旨在确定剪切力学在产生由影响人类的重要病原体制成的生物膜中的作用。 这将为预防和清除针对机械特性的生物膜的新方法奠定基础，从而造福社会。 今天，防止生物膜的方法集中在开发抵抗细菌附着或杀死细菌的表面上，但成功有限。成熟的生物膜通常抵抗处理，除了通过机械去除，并且生物膜的机械破碎也可以增加对常规抗生素的脆弱性。几乎没有人知道不同的基质材料如何控制生物膜的力学。这项研究将改善生物膜的预防和修复，并有利于公共卫生和基础设施，其中生物膜是一个问题，如在水处理厂的管道，石油运输管道。在第一个教育目标中开发的教育模块将与高中生物学、物理学和数学课程标准保持一致，提供对科学知识如何发展的经验性理解，并教授跨学科的核心概念。第二个教育目标将导致更好的策略，以改善长期本科STEM管道为传统和代表性不足的群体。铜绿假单胞菌是一种模式生物，具有良好的特征遗传学和分子生物学，也很容易形成生物膜，具有重要的工业和医学影响。将使用流变学测量生物膜力学。将对单个细菌和生物膜内的细菌施加受控应力，并测量所得信号传导、表型变化和生物膜发育。遗传操作将被用来阐明特定的基因产物如何有助于特定的机械性能和机械传感，信号，和生物膜的启动。研究目的是：（1）确定剪切力学在触发引发生物膜发展的信号中的作用-这将揭示阻碍机械感测并由此防止生物膜引发的表面的设计原理;（2）确定特定生物膜组分在促成成熟生物膜的机械弹性中的作用-这将导致可根据特定基质组成和机械性质调节的破坏和清除策略;（3）确定组成细菌对生物膜硬度和应变的机械感觉响应-这将指示如何降低生物膜动态适应的能力并增加其机械鲁棒性。 (1)研究目标1将导致一种新的生物膜预防模式，其靶向高度保守的信号传导机制，进化逃逸将是困难或不可能的。(2)研究目标2将为理解生物膜作为复合材料的力学提供一个新的框架。(3)研究目标3将导致生物膜如何作为多细胞，力敏感的“组织”的新知识。

项目成果

Assaying How Phagocytic Success Depends on the Elasticity of a Large Target Structure

• DOI: 10.1016/j.bpj.2019.08.043
• 发表时间: 2019-10-15
• 期刊: BIOPHYSICAL JOURNAL
• 影响因子: 3.4
• 作者: Davis-Fields, Megan;Bakhtiari, Layla A.;Gordon, Vernita D.
• 通讯作者: Gordon, Vernita D.

High-throughput assays show the timescale for phagocytic success depends on the target toughness

• DOI: 10.1063/5.0057071
• 发表时间: 2021-09-01
• 期刊: BIOPHYSICS REVIEWS
• 作者: Bakhtiari, Layla A.;Wells, Marilyn J.;Gordon, Vernita D.
• 通讯作者: Gordon, Vernita D.

Specific Disruption of Established Pseudomonas aeruginosa Biofilms Using Polymer-Attacking Enzymes

• DOI: 10.1021/acs.langmuir.9b02188
• 发表时间: 2020-02-18
• 期刊: LANGMUIR
• 影响因子: 3.9
• 作者: Kovach, Kristin N.;Fleming, Derek;Gordon, Vernita Diane
• 通讯作者: Gordon, Vernita Diane

Principles and Applications of Biological Membrane Organization

生物膜组织原理及应用

• DOI: 10.1146/annurev-biophys-121219-081637
• 发表时间: 2020
• 期刊: Annual Review of Biophysics
• 影响因子: 12.4
• 作者: Zeno, Wade F.;Day, Kasey J.;Gordon, Vernita D.;Stachowiak, Jeanne C.
• 通讯作者: Stachowiak, Jeanne C.