We are what we eat : identifying a regulatory crosstalk between central carbon metabolism and cell division in bacteria

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Cell division is crucial to the survival and propagation of all living organisms. In bacteria, the process of cell division is initiated by the formation of the cytokinetic Z ring, made up of the tubulin-like protein FtsZ, at the cell centre (midcell). Research into the control of Z ring positioning in the well-studied rod-shaped bacteria has focused on two main regulatory systems, the Min system and nucleoid occlusion. However, an aspect of cell division control that remains often overlooked is the need to coordinate cell cycle events with the nutrient availability. Central Carbon Metabolism (CCM), being the entry point for almost all the raw materials required for cellular growth and proliferation, forms the hub for coordinating nutrient availability to cell growth, size and the division process. Our lab recently identified a novel link between the central carbon metabolic pathway of glycolysis and cell division, wherein disrupting glycolysis by deleting the pyruvate kinase (𝘱𝘺𝘬) enzyme was shown to affect the correct positioning of the Z ring at the cell centre, such that 1/3ʳᡈ of the Z rings formed at acentral positions. Interestingly, the addition of pyruvate (the end product of the pyruvate kinase reaction), alleviated this Z ring positioning defect of βˆ†π˜±π˜Ίπ˜¬ cells. Pyruvate is a metabolite that lies at the intersection of many metabolic pathways, raising the possibility of any of the potential metabolic fates of pyruvate being actually responsible for the Z ring positioning rescue of βˆ†π˜±π˜Ίπ˜¬ cells. The experimental results presented in this thesis confirm that pyruvate, and not any of its potential metabolic fates, is the key metabolite coordinating CCM to cell division in π˜‰π˜’π˜€π˜ͺ𝘭𝘭𝘢𝘴 𝘴𝘢𝘣𝘡π˜ͺ𝘭π˜ͺ𝘴. Furthermore, this thesis also provide evidence for the role of DNA replication and nucleotide synthesis in the Z ring positioning defect of βˆ†π˜±π˜Ίπ˜¬ cells. Collectively, the work presented here demonstrates the importance of one specific metabolite - pyruvate, in maintaining the coordination between the cellular events of division, metabolism and DNA replication in π˜‰. 𝘴𝘢𝘣𝘡π˜ͺ𝘭π˜ͺ𝘴; which leads to the hypothesis that pyruvate might be acting as a signaling molecule to synchronize cell cycle events with the nutrient availability.
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