Department of Biological Regulation, Weizmann Institute of Science, 7610001 Rehovot, Israel.
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, 84105 Beer-Sheva, Israel.
Science. 2021 Jan 22;371(6527):400-405. doi: 10.1126/science.aba8026.
Key to the success of intracellular pathogens is the ability to sense and respond to a changing host cell environment. Macrophages exposed to microbial products undergo metabolic changes that drive inflammatory responses. However, the role of macrophage metabolic reprogramming in bacterial adaptation to the intracellular environment has not been explored. Here, using metabolic profiling and dual RNA sequencing, we show that succinate accumulation in macrophages is sensed by intracellular Typhimurium ( Tm) to promote antimicrobial resistance and type III secretion. Tm lacking the succinate uptake transporter DcuB displays impaired survival in macrophages and in mice. Thus, Tm co-opts the metabolic reprogramming of infected macrophages as a signal that induces its own virulence and survival, providing an additional perspective on metabolic host-pathogen cross-talk.
细胞内病原体成功的关键是能够感知和响应宿主细胞环境的变化。巨噬细胞暴露于微生物产物后会发生代谢变化，从而引发炎症反应。然而，巨噬细胞代谢重编程在细菌适应细胞内环境中的作用尚未得到探索。在这里，我们使用代谢组学和双 RNA 测序技术，表明鼠伤寒沙门氏菌（ Tm）通过感应巨噬细胞中的琥珀酸积累来促进其对微生物的抵抗力和 III 型分泌。缺乏琥珀酸摄取转运蛋白 DcuB 的 Tm 在巨噬细胞和小鼠中存活能力下降。因此， Tm 利用被感染巨噬细胞的代谢重编程作为信号来诱导自身的毒力和存活，为代谢宿主-病原体相互作用提供了一个新视角。
