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首页> 外文期刊>mSphere >Blocks in Tricarboxylic Acid Cycle of Salmonella enterica Cause Global Perturbation of Carbon Storage, Motility, and Host-Pathogen Interaction
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Blocks in Tricarboxylic Acid Cycle of Salmonella enterica Cause Global Perturbation of Carbon Storage, Motility, and Host-Pathogen Interaction

机译：沙门氏菌的三羧酸循环中的嵌段肠道导致碳储存，运动和宿主 - 病原体相互作用的全局扰动

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The tricarboxylic acid (TCA) cycle is a central metabolic hub in most cells. Virulence functions of bacterial pathogens such as facultative intracellular Salmonella enterica serovar Typhimurium ( S . Typhimurium) are closely connected to cellular metabolism. During systematic analyses of mutant strains with defects in the TCA cycle, a strain deficient in all fumarase isoforms (Δ fumABC ) elicited a unique metabolic profile. Alongside fumarate, S . Typhimurium Δ fumABC accumulates intermediates of the glycolysis and pentose phosphate pathway. Analyses by metabolomics and proteomics revealed that fumarate accumulation redirects carbon fluxes toward glycogen synthesis due to high (p)ppGpp levels. In addition, we observed reduced abundance of CheY, leading to altered motility and increased phagocytosis of S . Typhimurium by macrophages. Deletion of glycogen synthase restored normal carbon fluxes and phagocytosis and partially restored levels of CheY. We propose that utilization of accumulated fumarate as carbon source induces a status similar to exponential- to stationary-growth-phase transition by switching from preferred carbon sources to fumarate, which increases (p)ppGpp levels and thereby glycogen synthesis. Thus, we observed a new form of interplay between metabolism of S . Typhimurium and cellular functions and virulence. IMPORTANCE We performed perturbation analyses of the tricarboxylic acid cycle of the gastrointestinal pathogen Salmonella enterica serovar Typhimurium. The defect of fumarase activity led to accumulation of fumarate but also resulted in a global alteration of carbon fluxes, leading to increased storage of glycogen. Gross alterations were observed in proteome and metabolome compositions of fumarase-deficient Salmonella . In turn, these changes were linked to aberrant motility patterns of the mutant strain and resulted in highly increased phagocytic uptake by macrophages. Our findings indicate that basic cellular functions and specific virulence functions in Salmonella critically depend on the proper function of the primary metabolism.
机译：三羧酸（TCA）循环是大多数细胞中的中央代谢毂。细菌病原体的毒力函数如兼性细胞内沙门氏菌肠道肠道培序列（S.培氏毒蕈类）与细胞代谢密切相关。在TCA循环中具有缺陷的突变菌株的系统分析中，缺乏所有富马酸酶同种型（ΔFumABC）的菌株引发了独特的代谢曲线。和富马酸盐一起。 TyphimuriumδFumabc积累糖酵解和戊糖磷酸途径的中间体。由代谢组和蛋白质组学分析显示，由于高（P）PPGPP水平，富马酸盐累积将碳通量重定向碳通孔对糖原合成。此外，我们观察到咽部的丰富度降低，导致动力改变和吞噬症的吞噬作用增加。巨噬细胞的伤寒。缺失糖原合成酶恢复正常的碳通量和吞噬作用，部分恢复的Chey水平。我们提出利用累积的富马酸碳作为碳源，通过从优选的碳源切换到富马酸盐来诱导与稳定生长相转变相似的状态，这增加（P）PPGPP水平并从而糖合成。因此，我们观察了S的新陈代谢之间的一种新形式的相互作用。刺血管和细胞功能和毒力。重要性我们对胃肠道肠道肠道毒蕈氏菌肠道肠杆菌的三羧酸周期进行了扰动分析。富马酶活性的缺陷导致富马酸盐的积累，但也导致碳通量的全局改变，导致糖原的储存增加。在富马酶缺陷型沙门氏菌的蛋白质组和代谢组合物中观察到总改变。反过来，这些变化与突变菌株的异常运动模式相关联，并通过巨噬细胞产生高度增加的吞噬作用。我们的研究结果表明，沙门氏菌中的基本细胞功能和特异性毒力功能均依赖于主要代谢的适当功能。

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