A thermal fuse in methionine biosynthesis arrests growth and protects Escherichia coli at elevated temperatures

Abstract Microorganisms sense hazardous conditions and respond appropriately to maximize their survival. Adaptive stress resistance in microbes is mostly attributed to the expression of stress response genes, such as heat shock proteins, which prevent deterioration of cellular material. Here, we report a novel response of E. coli to heat stress: induction of a growth-arrested state, caused by degradation of an enzyme in the methionine biosynthesis pathway (MetA). We show that growth arrest has a direct benefit for survival at high temperatures; it protects cells when temperatures rise beyond 50oC, increasing the survival chances by over 1000-fold. Using a combination of experiments and mathematical modelling, we show that degradation of MetA leads to the coexistence of growing and non-growing cells, allowing microbes to bet-hedge between continued growth if conditions remain bearable and survival if conditions worsen. We test our model experimentally and verify quantitatively how protein expression, degradation rates and environmental stresses affect the partitioning between growing and non-growing cells. Because growth arrest can be abolished with simple mutations, such as point mutations of MetA and knock-outs of proteases, we interpret the breakdown of methionine synthesis as a system that has evolved to disintegrate at high temperature and shut off growth, analogous to ‘thermal fuses’ used in engineering to shut off electricity when the device could be damaged by overheating.