Dichotomous metabolism of Enterococcus faecalis induced by haematin starvation modulates colonic gene expression.
Dichotomous metabolism of Enterococcus faecalis induced by haematin starvation modulates colonic gene expression.
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DOI：
10.1099/jmm.0.47798-0
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发表时间：
2008-10
影响因子：
3
通讯作者：
Huycke MM
中科院分区：
文献类型：
--
作者：
Allen TD;Moore DR;Wang X;Casu V;May R;Lerner MR;Houchen C;Brackett DJ;Huycke MM
粪肠球菌是一种肠道共生菌，不能合成卟啉，仅在提供外源性血红素时表达功能性呼吸链。在缺乏血红素的情况下，E.粪球菌恢复到发酵代谢并产生可损伤上皮细胞DNA的细胞外超氧化物。结肠粘膜对血红素饥饿的E。通过基因芯片鉴定粪肠球菌。E.使用保持组织结构和体内平衡的外科结扎模型将粪肠球菌接种到小鼠结肠中。将粘膜暴露于血红蛋白饥饿的大肠杆菌。faecalis中，并与由用血红素生长的相同菌株组成的对照进行比较。在接种后1小时，6个粘膜基因受到差异调节，在6小时增加到42个基因。在6小时时，鉴定出高度显著的生物相互作用网络，其功能包括NF-κB信号传导、凋亡和细胞周期调节。苏木精和伊红染色显示结肠活检无组织学异常。然而，免疫组织化学染色检测组织巨噬细胞中NF-κB活化，使用针对p65的核定位序列和针对鼠巨噬细胞的F4/80标记的抗体。同样，血红素饥饿的E.粪肠杆菌在体外强烈激活小鼠巨噬细胞中的NF-κB。此外，原代和转化的结肠上皮细胞在体外暴露于血红素饥饿的E.粪便。这种细胞周期检查点的调节是由于血红素饥饿的E.粪便。这些结果表明，E.粪肠球菌可显著调节结肠粘膜中与炎症、凋亡和细胞周期调节相关的途径的基因表达。
Enterococcus faecalis is an intestinal commensal that cannot synthesize porphyrins and only expresses a functional respiratory chain when provided exogenous hematin. In the absence of hematin, E. faecalis reverts to fermentative metabolism and produces extracellular superoxide that can damage epithelial cell DNA. The acute response of the colonic mucosa to hematin-starved E. faecalis was identified by gene array. E. faecalis was inoculated into murine colons using a surgical ligation model that preserved tissue architecture and homeostasis. The mucosa was exposed to hematin-starved E. faecalis and compared to a control consisting of the same strain grown with hematin. At 1 hour post-inoculation six mucosal genes were differentially regulated and this increased to 42 genes at 6 hours. At 6 hours a highly significant biological interaction network was identified with functions that included NF-κB signaling, apoptosis, and cell cycle regulation. Colon biopsies showed no histological abnormalities by hematoxylin and eosin staining. Immunohistochemical staining, however, detected NF-κB activation in tissue macrophages using antibodies to the nuclear localization sequence for p65 and the F4/80 marker for murine macrophages. Similarly, hematin-starved E. faecalis strongly activated NF-κB in murine macrophages in vitro. Furthermore, primary and transformed colonic epithelial cells activated the G2/M checkpoint in vitro following exposure to hematin-starved E. faecalis. Modulation of this cell cycle checkpoint was due to extracellular superoxide produced as a result of the respiratory block in hematin-starved E. faecalis. These results demonstrate that the uniquely dichotomous metabolism of E. faecalis can significantly modulate gene expression in the colonic mucosa for pathways associated with inflammation, apoptosis, and cell cycle regulation.
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影响因子：
6
作者：
Balish, E;Warner, T
通讯作者：
Warner, T
影响因子：
4.7
作者：
Huycke, MM;Abrams, V;Moore, DR
通讯作者：
Moore, DR
影响因子：
6.4
作者：
Huycke, MM;Joyce, W;Wack, MF
通讯作者：
Wack, MF
影响因子：
4.2
作者：
Augenlicht, LH;Mariadason, JM;Velcich, A
通讯作者：
Velcich, A
影响因子：
2.6
作者：
BENNO, Y;SUZUKI, K;MITSUOKA, T
通讯作者：
MITSUOKA, T