Mechanoregulation in the Maintenance of the Bacterial Cell Wall

这个项目将研究细菌对机械力的生物反应。细菌是地球上最丰富的生命形式。细菌可以在人类以及食物供应中的动植物中引起疾病。然而，一些细菌，如益生菌，对人类、动物和植物的健康有益(例如，益生菌)，而其他一些细菌则用于食品和药品的生产。抗生素被用来清除致病细菌。抗生素发挥作用的一种常见方式是导致细菌细胞膜的机械故障--即导致细胞破裂并死亡。然而，环境中越来越多的抗药性细菌菌株，对健康和食品生产构成了挑战。这个项目的目标是了解细菌如何抵抗通常会导致它们破裂的机械力。我们探索了一种新的想法，即细菌可以感觉到细胞膜和细胞壁的过度拉伸，并通过加厚和加强细胞壁来防止死亡。此外，该项目还包括一个项目，旨在通过吸收本科生研究人员并与服务于专业社会的少数人合作，扩大对科学和工程的参与。这项工作使用了一种新型的微流控系统，在单个细菌的细胞膜内产生机械应力，并使用传统和单分子显微镜观察响应。我们关注的是VxrAB(也被称为WigKR)，它是霍乱弧菌中的一个双组分信号系统，参与细菌细胞壁的重塑和动态平衡。这项工作的研究目标是1)确定机械应力和应变在刺激VxrAB系统和由此产生的细胞壁生物发生中的作用；2)确定细胞被膜机械性质响应VxrAB信号的变化。这项工作的教育目标包括：1)带头努力扩大研究实验室内任职人数不足的群体成员对科学的参与；2)在全国会议上组织一次会议，加强来自任职人数不足背景的学生的生物工程事业。该项目由土木、机械和制造创新部门的生物力学和机械生物学项目以及分子和细胞生物科学部门的系统和合成生物学项目共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.