Mechanoregulation in the Maintenance of the Bacterial Cell Wall

维持细菌细胞壁的机械调节

• 批准号: 2055214
• 负责人: Christopher Hernandez
• 金额: $ 43万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2055214&HistoricalAwards=false
• 关键词: Mechanoregulation; Maintenance; Bacterial; Cell; Wall

This project will study the biological response to mechanical forces in bacteria. Bacteria are the most abundant form of life on Earth. Bacteria can cause disease in humans as well as in animals and plants in the food supply. However, some bacteria such as probiotics are beneficial to the health of humans, animals, and plants (e.g. probiotics) and others are used in production of food and pharmaceuticals. Antibiotics are used to remove disease-causing bacteria. A common way that antibiotics work is to cause the mechanical failure of the bacterial cell envelope – i.e. causing the cells to burst open and die. However, antibiotic resistant strains of bacteria are increasingly abundant in the environment, presenting a challenge to health and food production. The goal of this project is to understand how bacteria resist the mechanical forces that would normally cause them to burst. We explore the novel idea that bacteria can sense excessive stretching in their cell membranes and cell wall and respond to this sensation by thickening and strengthening their cell walls to prevent death. Additionally, the project involves a project to broaden participation in science and engineering through inclusion of undergraduate researchers and work with a minority serving professional society. The work uses a novel microfluidic system to generate mechanical stress within the cell envelope of individual bacteria and observe the response using conventional and single molecule microscopy. We focus on VxrAB (also referred to as WigKR), a two-component signaling system in Vibrio cholerae which is involved in the remodeling and homeostasis of the bacterial cell wall. The research objectives of this work are to 1) Determine the role of mechanical stress and strain in stimulating the VxrAB system and the resulting cell wall biogenesis; and 2) Determine the changes in cell envelope mechanical properties in response to VxrAB signaling. The educational objectives of this work include: 1) lead efforts to broaden participation in science by members of underrepresented groups within investigator laboratories and 2) organize a session at a national meeting to enhance bioengineering careers of students from underrepresented backgrounds. This project is co-funded by the Biomechanics and Mechanobiology program in the Division of Civil, Mechanical, and Manufacturing Innovation, and the Systems and Synthetic Biology program in the Division of Molecular and Cellular BiosciencesThis 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.

该项目将研究细菌中对机械力的生物学反应。细菌是地球上最丰富的生命形式。细菌会引起人类以及动物和植物的疾病。但是，某些细菌（例如益生菌）对人类，动物和植物（例如益生菌）的健康有益于食品和药品的生产。抗生素用于去除引起疾病的细菌。抗生素起作用的一种常见方法是导致细菌细胞包膜的机械故障 - 即导致细胞破裂并死亡。然而，在环境中，细菌的抗生素抗性菌株越来越丰富，对健康和粮食生产构成了挑战。该项目的目的是了解细菌如何抵抗通常会导致它们破裂的机械力。我们探讨了一种新颖的想法，即细菌可以感觉到其细胞膜和细胞壁上过度拉伸，并通过增厚和加强其细胞壁以防止死亡来应对这种感觉。此外，该项目涉及通过包括本科研究人员并与为专业社会服务的少数群体合作，以扩大对科学和工程的参与。该工作使用新型的微流体系统在单个细菌的细胞包膜内产生机械应力，并使用常规和单分子显微镜观察反应。我们专注于VXRAB（也称为Wigkr），这是一种在蛇形霍乱中的两个组件信号系统，涉及细菌细胞壁的重塑和稳态。这项工作的研究目标是1）确定机械应力和应变在刺激VXRAB系统和所得细胞壁生物发生中的作用； 2）确定响应VXRAB信号传导的细胞包膜机械性能的变化。这项工作的教育对象包括：1）领导努力，以扩大研究人员实验室中代表性不足的团体成员对科学的参与，以及2）在全国会议上组织一次会议，以增强来自代表性不足的学生的生物工程学职业。该项目是由生物力学和机械生物学计划共同资助了民用，机械和制造创新部的，以及分子和蜂窝biosciencesthis奖的系统和合成生物学计划反映了NSF的法规任务，并认为通过基金会的知识优点和广泛的criter scritia crietia criters criter criter criters criter criter criter criteria criter criter criter criter criter criter criter criteria crietia criteria criteria crietia criter criteria criteria scriter criteria criteria crietia cribitia均反映了该奖项。

项目成果

Mechanical stimuli activate gene expression via a cell envelope stress sensing pathway.

• DOI: 10.1038/s41598-023-40897-w
• 发表时间: 2023-08-26
• 期刊: Scientific reports
• 影响因子: 4.6

Solute Transport in Engineered Living Materials Using Bone‐Inspired Microscale Channel Networks

使用骨启发的微尺度通道网络进行工程活性材料中的溶质运输

• DOI: 10.1002/adem.202301032
• 发表时间: 2023
• 期刊: Advanced Engineering Materials
• 影响因子: 3.6
• 作者: van Wijngaarden, Ellen W.;Bratcher, Samantha;Lewis, Karl J.;Hernandez, Christopher J.
• 通讯作者: Hernandez, Christopher J.