A Comparison of the ATP Generating Pathways Used by S. Typhimurium to Fuel Replication within Human and Murine Macrophage and Epithelial Cell Lines.
A Comparison of the ATP Generating Pathways Used by S. Typhimurium to Fuel Replication within Human and Murine Macrophage and Epithelial Cell Lines.
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DOI：
10.1371/journal.pone.0150687
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Thompson A
中科院分区：
文献类型：
--
作者：
Garcia-Gutierrez E;Chidlaw AC;Le Gall G;Bowden SD;Tedin K;Kelly DJ;Thompson A
受感染宿主细胞内鼠伤寒沙门氏菌的代谢在毒力中发挥着重要作用，因为它能够实现细胞内增殖和传播并影响先天免疫反应。鼠伤寒沙门氏菌细胞内复制的一个基本要求是需要再生 ATP。用于满足这一要求的代谢途径是本研究的主题。对于感染模型，我们使用人和鼠上皮细胞和巨噬细胞系。上皮细胞系是 mICc12（一种永生化的小鼠结肠肠上皮细胞系，显示出原代上皮细胞系的许多特征）和 HeLa 细胞。模型巨噬细胞系是THP-1A人单核细胞/巨噬细胞和RAW 264.7鼠巨噬细胞。使用突变方法与外代谢组学分析相结合，我们发现发酵代谢和无氧呼吸在所研究的任何细胞系的能量产生中都不起主要作用。相反，我们发现乙酸盐和乳酸的过度代谢是鼠伤寒沙门氏菌满足其能量需求的首要途径。
The metabolism of S. Typhimurium within infected host cells plays a fundamental role in virulence since it enables intracellular proliferation and dissemination and affects the innate immune response. An essential requirement for the intracellular replication of S. Typhimurium is the need to regenerate ATP. The metabolic route used to fulfil this requirement is the subject of the present study. For infection models we used human and murine epithelial and macrophage cell lines. The epithelial cell lines were mICc12, a transimmortalised murine colon enterocyte cell line that shows many of the characteristics of a primary epithelial cell line, and HeLa cells. The model macrophage cell lines were THP-1A human monocyte/macrophages and RAW 264.7 murine macrophages. Using a mutational approach combined with an exometabolomic analysis, we showed that neither fermentative metabolism nor anaerobic respiration play major roles in energy generation in any of the cell lines studied. Rather, we identified overflow metabolism to acetate and lactate as the foremost route by which S. Typhimurium fulfils its energy requirements.