A Second Role for the Second Messenger Cyclic-di-GMP in E. coli: Arresting Cell Growth by Altering Metabolic Flow.
A Second Role for the Second Messenger Cyclic-di-GMP in E. coli: Arresting Cell Growth by Altering Metabolic Flow.
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C-di-GMP主要控制细菌从运动到静止的转变。双鸟苷环化酶(DGC)催化两个GTP分子合成c-di-GMP。通常，细菌编码多个DGC，这些DGC被特定的环境信号激活。它们的催化活性受c-di-GMP与自身抑制位点(I-位点)结合的调节。YfiN是一种保守的内膜DGC，缺乏这些位点。相反，YfiN的活性直接被周质YfiR抑制，而YfiR被氧化还原压力灭活。在大肠杆菌中，额外的包膜压力会导致YfiN重新定位到中间细胞，通过与分裂机制的相互作用来抑制细胞分裂。在这里，我们报告了YfiN在大肠杆菌中的第三个活性，其中细胞生长受到抑制，而不会将YfiN重新定位到分裂位置。YfiN的这种作用只有在细菌培养在生糖碳源上时才能观察到，并且依赖于自身抑制位点的缺乏。I-Site功能的恢复可以缓解生长停滞表型，而在异源DGC中禁用这一功能会导致获得这一表型。受阻细胞对多种抗生素都有耐受性。我们表明，生长停滞的可能原因是c-di-GMP的快速合成耗尽了细胞内的GTP，解释了生长停滞依赖于在葡萄糖生产过程中消耗更多GTP的生糖碳源。这是第一个关于c-di-GMP通过改变代谢流介导的生长停滞的报道。
c-di-GMP primarily controls motile to sessile transitions in bacteria. Diguanylate cyclases (DGCs) catalyze the synthesis of c-di-GMP from two GTP molecules. Typically, bacteria encode multiple DGCs that are activated by specific environmental signals. Their catalytic activity is modulated by c-di-GMP binding to autoinhibitory sites (I-sites). YfiN is a conserved inner membrane DGC that lacks these sites. Instead, YfiN activity is directly repressed by periplasmic YfiR, which is inactivated by redox stress. In Escherichia coli, an additional envelope stress causes YfiN to relocate to the mid-cell to inhibit cell division by interacting with the division machinery. Here, we report a third activity for YfiN in E. coli, where cell growth is inhibited without YfiN relocating to the division site. This action of YfiN is only observed when the bacteria are cultured on gluconeogenic carbon sources, and is dependent on absence of the autoinhibitory sites. Restoration of I-site function relieves the growth-arrest phenotype, and disabling this function in a heterologous DGC causes acquisition of this phenotype. Arrested cells are tolerant to a wide range of antibiotics. We show that the likely cause of growth arrest is depletion of cellular GTP from run-away synthesis of c-di-GMP, explaining the dependence of growth arrest on gluconeogenic carbon sources that exhaust more GTP during production of glucose. This is the first report of c-di-GMP-mediated growth arrest by altering metabolic flow.
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影响因子：
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DOI：
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发表时间：
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