MetA is a "thermal fuse" that inhibits growth and protects Escherichia coli at elevated temperatures.
MetA is a "thermal fuse" that inhibits growth and protects Escherichia coli at elevated temperatures.
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DOI：
10.1016/j.celrep.2022.111290
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发表时间：
2022-08-30
期刊：
影响因子：
8.8
通讯作者：
Gerland, Ulrich
中科院分区：
文献类型：
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作者：
Schink, Severin J.;Gough, Zara;Biselli, Elena;Huiman, Mariel Garcia;Chang, Yu-Fang;Basan, Markus;Gerland, Ulrich
微生物的适应性应激抗性主要归因于应激反应基因的表达，例如热休克蛋白，其防止细胞物质的劣化。在这里，我们报告的响应E。大肠杆菌对热应激的反应，热应激是由甲硫氨酸生物合成途径中的酶（Meta）降解引起的，导致生长抑制状态的诱导。虽然Meta降解对增殖有害，并且在高温下可能导致甲硫氨酸营养缺陷型，但我们表明，所产生的生长抑制对高温下的存活具有直接益处;当温度升高超过50°C时，它可以保护细胞，使存活机会增加1000倍以上。使用实验和数学建模的组合，我们表明，降解的Meta导致生长和非生长细胞的共存，使微生物之间的持续增长，如果条件仍然恶劣和生存，如果条件恶化。我们通过实验测试我们的模型，并定量验证蛋白质表达，降解速率和环境压力如何影响生长和非生长细胞之间的分区。因为生长抑制可以通过简单的突变来消除，例如Meta的点突变和蛋白酶的敲除，我们将蛋氨酸合成的分解解释为一种在高温下分解并关闭生长的系统，类似于工程中使用的“热熔断器”，当设备可能因过热而损坏时关闭电力。
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 response of E. coli to heat stress, caused by degradation of an enzyme in the methionine biosynthesis pathway (MetA), leading to the induction of a growth-inhibited state.. While MetA degradation is detrimental for proliferation and can lead to methionine auxotrophy at high temperatures, we show that the resulting growth inhibition has a direct benefit for survival at high temperatures; it protects cells when temperatures rise beyond 50°C, 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 stressors affect the partitioning between growing and non-growing cells. Because growth inhibition 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.
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影响因子：
3.5
作者：
CHEREPANOV, PP;WACKERNAGEL, W
通讯作者：
WACKERNAGEL, W
DOI：
10.1073/pnas.1114477108
发表时间：
2011-11-01
影响因子：
11.1
作者：
Dill, Ken A.;Ghosh, Kingshuk;Schmit, Jeremy D.
通讯作者：
Schmit, Jeremy D.
DOI：
10.1073/pnas.93.10.5116
发表时间：
1996-05-14
影响因子：
11.1
作者：
Davidson, JF;Whyte, B;Schiestl, RH
通讯作者：
Schiestl, RH
大肠杆菌K-12的构造框架，单基因敲除突变体：Keio Collection。
影响因子：
9.9
作者：
通讯作者：
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影响因子：
3.7
作者：
通讯作者：
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