Pseudomonas protegens H78 produces multiple secondary metabolites, including antibiotics and iron carriers. The guanosine pentaphosphate or tetraphosphate ((p)ppGpp)-mediated stringent response is utilized by bacteria to survive during nutritional starvation and other stresses. RelA/SpoT homologues are responsible for the biosynthesis and degradation of the alarmone (p)ppGpp. Here, we investigated the global effect of relA/spoT dual deletion on the transcriptomic profiles, physiology, and metabolism of P. protegens H78 grown to mid- to late log phase. Transcriptomic profiling revealed that relA/spoT deletion globally upregulated the expression of genes involved in DNA replication, transcription, and translation; amino acid metabolism; carbohydrate and energy metabolism; ion transport and metabolism; and secretion systems. Bacterial growth was partially increased, while the cell survival rate was significantly reduced by relA/spoT deletion in H78. The utilization of some nutritional elements (C, P, S, and N) was downregulated due to relA/spoT deletion. In contrast, relA/spoT mutation globally inhibited the expression of secondary metabolic gene clusters (plt, phl, prn, ofa, fit, pch, pvd, and has). Correspondingly, antibiotic and iron carrier biosynthesis, iron utilization, and antibiotic resistance were significantly downregulated by the relA/spoT mutation. This work highlights that the (p)ppGpp-mediated stringent response regulatory system plays an important role in inhibiting primary metabolism and activating secondary metabolism in P. protegens.

中文翻译：

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（p）ppGpp介导的严格反应调节系统整体上抑制了假单胞菌蛋白H78中的初级代谢并激活了次级代谢。

假单胞菌蛋白H78产生多种次级代谢产物，包括抗生素和铁载体。细菌利用五磷酸鸟苷或四磷酸鸟嘌呤（（p）ppGpp）介导的严格反应在营养饥饿和其他压力下生存。RelA / SpoT同源物负责警报蛋白（p）ppGpp的生物合成和降解。在这里，我们调查了relA / spoT双重缺失对生长到对数中期到中晚期的P. protegens H78的转录组概况，生理和代谢的总体影响。转录组分析表明，relA / spoT缺失在全球范围内上调了涉及DNA复制，转录和翻译的基因的表达；氨基酸代谢 碳水化合物和能量代谢；离子运输和代谢；和分泌系统。H78中的relA / spoT缺失使细菌的生长部分增加，而细胞存活率却大大降低。由于relA / spoT缺失，一些营养元素（C，P，S和N）的利用被下调。相反，relA / spoT突变总体上抑制了次级代谢基因簇（plt，phl，prn，ofa，fit，pch，pvd和has）的表达。相应地，relA / spoT突变显着下调了抗生素和铁载体的生物合成，铁的利用以及对抗生素的抗性。这项工作强调了（p）ppGpp介导的严格反应调节系统在抑制蛋白质原核生物的初级代谢和激活次级代谢中起着重要作用。由于relA / spoT缺失，一些营养元素（C，P，S和N）的利用被下调。相反，relA / spoT突变总体上抑制了次级代谢基因簇（plt，phl，prn，ofa，fit，pch，pvd和has）的表达。相应地，relA / spoT突变显着下调了抗生素和铁载体的生物合成，铁的利用以及对抗生素的抗性。这项工作凸显了（p）ppGpp介导的严格反应调节系统在抑制蛋白质假单胞菌的主要代谢和激活次要代谢中起着重要作用。由于relA / spoT缺失，一些营养元素（C，P，S和N）的利用被下调。相反，relA / spoT突变总体上抑制了次级代谢基因簇（plt，phl，prn，ofa，fit，pch，pvd和has）的表达。相应地，relA / spoT突变显着下调了抗生素和铁载体的生物合成，铁的利用以及对抗生素的抗性。这项工作强调了（p）ppGpp介导的严格反应调节系统在抑制蛋白质原核生物的初级代谢和激活次级代谢中起着重要作用。相应地，relA / spoT突变显着下调了抗生素和铁载体的生物合成，铁的利用以及对抗生素的抗性。这项工作强调了（p）ppGpp介导的严格反应调节系统在抑制蛋白质原核生物的初级代谢和激活次级代谢中起着重要作用。相应地，relA / spoT突变显着下调了抗生素和铁载体的生物合成，铁的利用以及对抗生素的抗性。这项工作强调了（p）ppGpp介导的严格反应调节系统在抑制蛋白质原核生物的初级代谢和激活次级代谢中起着重要作用。