IISER MOHALI

Abstract: For optimal survival, living cells must synchronize their growth and division with nutrient availability and metabolic activity. Bacteria, for instance, exhibit remarkable metabolic flexibility that allows them to thrive in diverse nutrient conditions. However, the underlying mechanisms that bacterial cells utilize to coordinate their cell cycle with nutrient availability and metabolism remain poorly understood. Interestingly, in the dimorphic bacterium Caulobacter crescentus, an oscillating cytosolic redox plays a crucial role in regulating cell cycle progression by modulating the activity of key cell cycle regulators. A genetic screen, for factors influencing cell cycle progression, uncovered mutations in regulatory elements of metabolic enzymes and their impact on cytosolic redox oscillations. These mutations highlighted metabolism as a key determinant of the redox dynamics. To understand the precise metabolic pathways influencing the cytosolic redox state, we resorted to mass spectrometry-based metabolomic analysis and validated our findings using genetics. Our study has uncovered a hierarchical metabolic network, rewiring of which leads to cell cycle stage-specific arrests. Together, our findings put forth an unorthodox regulatory principle that orchestrates cell cycle progression in response to metabolism in bacteria.