Lowering GTP Level Increases Survival of Amino Acid Starvation but Slows Growth Rate for Bacillus subtilis Cells Lacking (p)ppGpp
Lowering GTP Level Increases Survival of Amino Acid Starvation but Slows Growth Rate for Bacillus subtilis Cells Lacking (p)ppGpp
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DOI：
10.1128/jb.01471-14
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发表时间：
2014-06-01
影响因子：
3.2
通讯作者：
Wang, Jue D.
中科院分区：
文献类型：
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作者：
Bittner, Alycia N.;Kriel, Allison;Wang, Jue D.
细菌细胞感知外部营养物质的可利用性来调节大分子的合成，从而调节它们的生长。在革兰氏阳性细菌枯草芽孢杆菌中，饥饿诱导的核苷酸（p）ppGpp负调节GTP水平，以抵抗营养应激并维持生长期间的GTP稳态。在这里，我们定量研究了GTP水平之间的关系，生存的氨基酸饥饿，生长速度时，GTP合成是解偶联从其主要的稳态调节，（p）ppGpp。我们分析了缺乏（p）ppGpp的细胞的生长和核苷酸水平，发现用非功能性氨基酸类似物治疗的存活率与生长速率和GTP水平呈负相关。GTP水平的操纵以正剂量依赖性方式调节这些细胞的指数生长速率，使得增加GTP水平增加生长速率。然而，超过阈值的GTP水平的积累抑制生长，表明毒性作用。引人注目的是，腺嘌呤通过防止GTP在缺乏（p）ppGpp的细胞中积累来抵消GTP应激。我们的研究结果强调了保持适当水平的GTP以最大限度地提高生长的重要性：细胞可以通过降低GTP水平来生存氨基酸饥饿，这是以生长为代价的，而（p）ppGpp可以通过调节GTP水平快速调整营养应激，从而最大限度地提高适应性。
Bacterial cells sense external nutrient availability to regulate macromolecular synthesis and consequently their growth. In the Gram-positive bacterium Bacillus subtilis, the starvation-inducible nucleotide (p)ppGpp negatively regulates GTP levels, both to resist nutritional stress and to maintain GTP homeostasis during growth. Here, we quantitatively investigated the relationship between GTP level, survival of amino acid starvation, and growth rate when GTP synthesis is uncoupled from its major homeostatic regulator, (p)ppGpp. We analyzed growth and nucleotide levels in cells that lack (p)ppGpp and found that their survival of treatment with a nonfunctional amino acid analog negatively correlates with both growth rate and GTP level. Manipulation of GTP levels modulates the exponential growth rate of these cells in a positive dose-dependent manner, such that increasing the GTP level increases growth rate. However, accumulation of GTP levels above a threshold inhibits growth, suggesting a toxic effect. Strikingly, adenine counteracts GTP stress by preventing GTP accumulation in cells lacking (p)ppGpp. Our results emphasize the importance of maintaining appropriate levels of GTP to maximize growth: cells can survive amino acid starvation by decreasing GTP level, which comes at a cost to growth, while (p)ppGpp enables rapid adjustment to nutritional stress by adjusting GTP level, thus maximizing fitness.