Data from which the figures were made.

Detoxification, scavenging, and repair systems embody the archetypical antioxidant defenses of prokaryotic and eukaryotic cells. Metabolic rewiring also aids with the adaptation of bacteria to oxidative stress. Evolutionarily diverse bacteria combat the toxicity of reactive oxygen species (ROS) by actively engaging the stringent response, a stress program that controls many metabolic pathways at the level of transcription initiation via guanosine tetraphosphate and the α-helical DksA protein. Studies herein with Salmonella demonstrate that the interactions of structurally related, but functionally unique, α-helical Gre factors with the secondary channel of RNA polymerase elicit the expression of metabolic signatures that are associated with resistance to oxidative killing. Gre proteins both improve transcriptional fidelity of metabolic genes and resolve pauses in ternary elongation complexes of Embden–Meyerhof–Parnas (EMP) glycolysis and aerobic respiration genes. The Gre-directed utilization of glucose in overflow and aerobic metabolism satisfies the energetic and redox demands of Salmonella, while preventing the occurrence of amino acid bradytrophies. The resolution of transcriptional pauses in EMP glycolysis and aerobic respiration genes by Gre factors safeguards Salmonella from the cytotoxicity of phagocyte NADPH oxidase in the innate host response. In particular, the activation of cytochrome bd protects Salmonella from phagocyte NADPH oxidase-dependent killing by promoting glucose utilization, redox balancing, and energy production. Control of transcription fidelity and elongation by Gre factors represent important points in the regulation of metabolic programs supporting bacterial pathogenesis.

解毒、清除与修复系统构成原核与真核细胞的典型抗氧化防御体系。代谢重编程同样可辅助细菌适应氧化应激。进化上具有多样性的细菌通过主动激活严谨反应（stringent response）来抵御活性氧（reactive oxygen species，ROS）的毒性：该应激程序可通过四磷酸鸟苷与α螺旋DksA蛋白，在转录起始水平调控多条代谢通路。本研究以沙门氏菌为对象开展的实验证实，结构相关但功能独特的α螺旋Gre因子与RNA聚合酶（RNA polymerase）次级通道的相互作用，可诱导出与氧化杀伤抗性相关的代谢特征谱。Gre蛋白既能提升代谢基因的转录保真度，还能解除糖酵解（Embden–Meyerhof–Parnas，EMP）与有氧呼吸相关基因的三元延伸复合物中的转录暂停。Gre因子介导的溢流代谢与有氧代谢中的葡萄糖利用，既满足了沙门氏菌的能量与氧化还原需求，又可避免氨基酸缓养缺陷的产生。Gre因子解除EMP糖酵解与有氧呼吸基因的转录暂停，能够保护沙门氏菌免受宿主固有免疫应答中吞噬细胞NADPH氧化酶（phagocyte NADPH oxidase）的细胞毒性损伤。尤为关键的是，细胞色素bd（cytochrome bd）的激活可通过促进葡萄糖利用、维持氧化还原平衡与能量生成，使沙门氏菌免受吞噬细胞NADPH氧化酶依赖性杀伤。Gre因子对转录保真度与转录延伸的调控，是支撑细菌致病机制的代谢程序调控的重要靶点。