The stringent response plays a key role in Bacillus subtilis survival of fatty acid starvation
The stringent response plays a key role in Bacillus subtilis survival of fatty acid starvation
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DOI：
10.1111/mmi.13582
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发表时间：
2017-02-01
影响因子：
3.6
通讯作者：
Gueiros-Filho, Frederico J.
中科院分区：
文献类型：
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作者：
Pulschen, Andre A.;Sastre, Diego E.;Gueiros-Filho, Frederico J.
严格反应是保护细菌免受营养和环境胁迫的普遍适应机制。在脂质饥饿过程中严格反应的作用仅在革兰氏阴性菌中进行了研究。在这里，我们报告说，严格的反应也起着至关重要的作用，在适应模型革兰氏阳性枯草芽孢杆菌脂肪酸饥饿。B。缺乏所有三种（p）ppGpp-合成酶（Rel（Bs）、RelP和RelQ）或携带不再合成（p）ppGpp的RelBs变体的枯草芽孢杆菌在脂质饥饿时遭受生存力的极大损失。细胞膜完整性和功能的紊乱导致细胞活力丧失，而细胞膜电位的崩溃可能是导致死亡的原因。在脂饥饿的B中，虽然没有检测到（p）ppGpp的增加。在枯草芽孢杆菌中，我们观察到不能合成（p）ppGpp的菌株的GTP/ATP比率显著增加。用decoyinine牺牲性地降低GTP挽救了这些菌株的生存力，证实了低细胞内GTP对于营养应激的存活是重要的观察结果。总之，我们的研究结果表明，激活的严格响应的脂质饥饿是一个广泛保守的细菌的反应，（p）ppGpp的一个关键作用是耦合生物合成过程，如果不协调，成为有害的。
The stringent response is a universal adaptive mechanism to protect bacteria from nutritional and environmental stresses. The role of the stringent response during lipid starvation has been studied only in Gram-negative bacteria. Here, we report that the stringent response also plays a crucial role in the adaptation of the model Gram-positive Bacillus subtilis to fatty acid starvation. B. subtilis lacking all three (p) ppGpp-synthetases (Rel(Bs), RelP and RelQ) or bearing a RelBs variant that no longer synthesizes (p) ppGpp suffer extreme loss of viability on lipid starvation. Loss of viability is paralleled by perturbation of membrane integrity and function, with collapse of membrane potential as the likely cause of death. Although no increment of (p) ppGpp could be detected in lipid starved B. subtilis, we observed a substantial increase in the GTP/ATP ratio of strains incapable of synthesizing (p) ppGpp. Artificially lowering GTP with decoyinine rescued viability of such strains, confirming observations that low intracellular GTP is important for survival of nutritional stresses. Altogether, our results show that activation of the stringent response by lipid starvation is a broadly conserved response of bacteria and that a key role of (p) ppGpp is to couple biosynthetic processes that become detrimental if uncoordinated.