The Effects of Physical Forces on Bacteria Growth

物理力对细菌生长的影响

• 批准号: 1463084
• 负责人: Christopher Hernandez
• 金额: $ 40万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-15 至 2019-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1463084&HistoricalAwards=false
• 关键词: Effects; Physical; Forces; Bacteria; Growth

Bacteria are the most populous and variable form of life on Earth. Bacteria can cause disease in humans as well as in animals and plants important to the food supply and the environment. However, bacteria can also be beneficial (probiotics) and are used industrially in the production of pharmaceuticals. Controlling bacterial populations is necessary to prevent disease and for quality control in industrial settings. Antibiotics are used to kill bacteria, but the development of new antibiotics has not kept up with needs in medicine and industry. Most antibiotics kill bacteria by causing mechanical failure (rupture) of the cell wall leading to cell death. The research goal of this work is to determine how bacterial physiology changes in response to physical forces and to determine how well the bacterial cell wall resists physical forces. The educational objectives of the work are to lead a week-long workshop on the mechanical properties of biological materials targeted to high-school students from traditionally under-represented groups and contribute to other activities to broaden participation in science by members of under-represented groups within the institution and at the national level.Two hypotheses have been presented to explain the location and migration of intracellular proteins involved in cell wall synthesis: a) intracellular proteins involved in cell wall synthesis are directed by local cell wall curvature; and b) that cell wall synthesis proteins are directed to locations of increased cell wall stress/strain. This work addresses this question using a microfluidics-based mechanical testing approach that can modify mechanical stress/strain without large changes in cell wall curvature. The approach is novel in that it makes it possible to observe intracellular proteins in live bacteria while mechanical loading is being applied and does not require conditions of altered bacterial physiology (altered osmolality, filamentous growth, etc.). The research goals of this work are to: 1) Determine the relationship between mechanical strain, regions of cell wall growth and subcellular movement of a protein associated with cell wall synthesis (the MreB protein); and 2) Determine the entire mechanical strain field in the bacterial cell wall while load is applied.

细菌是地球上数量最多、变化最大的生命形式。细菌可以在人类以及对食物供应和环境很重要的动物和植物中引起疾病。然而，细菌也可以是有益的（益生菌），并在工业上用于生产药物。控制细菌种群对于预防疾病和工业环境中的质量控制是必要的。抗生素是用来杀死细菌的，但新抗生素的开发并没有跟上医学和工业的需求。大多数抗生素通过引起细胞壁的机械故障（破裂）导致细胞死亡来杀死细菌。这项工作的研究目标是确定细菌生理学如何响应物理力的变化，并确定细菌细胞壁抵抗物理力的能力。这项工作的教育目标是为传统上代表性不足的群体的高中生举办为期一周的关于生物材料机械性能的讲习班，并促进其他活动，以扩大代表性不足的群体成员对科学的参与。已经提出了两种假设来解释参与细胞内蛋白质的定位和迁移，细胞壁合成：a）参与细胞壁合成的细胞内蛋白由局部细胞壁曲率引导;和B）细胞壁合成蛋白被引导至细胞壁应力/应变增加的位置。 这项工作使用基于微流体的机械测试方法解决了这个问题，该方法可以修改机械应力/应变，而不会使细胞壁曲率发生大的变化。 该方法是新颖的，因为它使得可以在施加机械负载的同时观察活细菌中的细胞内蛋白质，并且不需要改变细菌生理学的条件（改变的渗透压、丝状生长等）。 这项工作的研究目标是：1）确定机械应变，细胞壁生长区域和与细胞壁合成相关的蛋白质（MreB蛋白）的亚细胞运动之间的关系; 2）确定施加载荷时细菌细胞壁中的整个机械应变场。

项目成果

Mechanical stress compromises multicomponent efflux complexes in bacteria

• DOI: 10.1073/pnas.1909562116
• 发表时间: 2019-12-17
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Genova, Lauren A.;Roberts, Melanie F.;Hernandez, Christopher J.
• 通讯作者: Hernandez, Christopher J.