Mechanoregulation in the Maintenance of the Bacterial Cell Wall

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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.