Salmonella profits from immunometabolism Extensive metabolic rewiring occurs in various immune cells during the course of infection. Whether these changes can be exploited by intracellular pathogens remains an open question. Rosenberg et al. report that infection with Salmonella enterica serovar Typhimurium (S. Tm) induces the accumulation of the metabolite succinate in macrophages (see the Perspective by Lynch and Lesser). This key intermediate in the citric acid cycle activates virulence genes in S. Tm, leading to microbial resistance. Moreover, the active transport of succinate through the C4-dicarboxylate transporter DcuB is required for S. Tm virulence and survival within macrophages. Sensing of citric acid cycle intermediates may more generally serve as a cue to initiate the resistance programs of intracellular pathogens. Science, this issue p. 400; see also p. 344 Salmonella co-opt host metabolic reprogramming needed for immune responses to induce virulence during intracellular infection. 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 Salmonella Typhimurium (S. Tm) to promote antimicrobial resistance and type III secretion. S. Tm lacking the succinate uptake transporter DcuB displays impaired survival in macrophages and in mice. Thus, S. 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.

中文翻译：

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宿主琥珀酸是细胞内感染期间沙门氏菌毒力的激活信号

沙门氏菌受益于免疫代谢 在感染过程中，各种免疫细胞中会发生广泛的代谢重组。这些变化是否可以被细胞内病原体利用仍然是一个悬而未决的问题。罗森伯格等。据报道，感染沙门氏菌鼠伤寒血清型（S. Tm）会诱导巨噬细胞中代谢物琥珀酸的积累（参见 Lynch 和 Lesser 的观点）。柠檬酸循环中的这个关键中间体激活 S. Tm 中的毒力基因，导致微生物抗性。此外，琥珀酸通过 C4-二羧酸转运蛋白 DcuB 的主动转运是 S. Tm 毒力和巨噬细胞内存活所必需的。对柠檬酸循环中间体的感知可能更普遍地作为启动细胞内病原体抗性程序的线索。科学，这个问题 400；另见第 344 沙门氏菌选择宿主代谢重编程是免疫反应在细胞内感染期间诱导毒力所需的。细胞内病原体成功的关键是能够感知和响应不断变化的宿主细胞环境。暴露于微生物产物的巨噬细胞会发生代谢变化，从而引发炎症反应。然而，尚未探索巨噬细胞代谢重编程在细菌适应细胞内环境中的作用。在这里，我们使用代谢分析和双 RNA 测序，表明巨噬细胞中的琥珀酸积累被细胞内鼠伤寒沙门氏菌 (S. Tm) 感知，以促进抗菌素耐药性和 III 型分泌。缺乏琥珀酸摄取转运蛋白 DcuB 的 S. Tm 在巨噬细胞和小鼠中显示出生存受损。因此，