Ethanolamine controls expression of genes encoding components involved in interkingdom signaling and virulence in enterohemorrhagic Escherichia coli O157:H7.
Ethanolamine controls expression of genes encoding components involved in interkingdom signaling and virulence in enterohemorrhagic Escherichia coli O157:H7.
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作者：
Kendall MM;Gruber CC;Parker CT;Sperandio V
细菌病原体必须能够识别宿主内适合定植的生态位，并成功与共生菌群竞争营养物质以建立感染。乙醇胺 (EA) 是哺乳动物和细菌膜的主要成分，被病原体用作胃肠道中的碳源和/或氮源。致命的人类病原体肠出血性大肠杆菌 O157:H7 (EHEC) 在肠道中使用 EA 作为氮源，作为相对于微生物菌群定植的竞争优势。在这里，我们表明 EA 不仅对氮代谢很重要，而且还用作细胞间信号传导中的信号分子，以激活肠出血性大肠杆菌中的毒力基因表达。不能作为氮源促进生长的浓度的 EA 可以激活 EHEC 毒力基因库的表达。 EutR 转录因子（已知为 EA 受体）仅部分负责这种调节，这表明还存在另一种 EA 受体。 EA 与新陈代谢、细胞间信号传导和发病机制的重要联系凸显了这样一个事实：微生物群落内的基本通讯方式依赖于能量产生和代谢物的处理。在这里，我们首次证明细菌病原体不仅利用 EA 作为代谢物，而且还利用 EA 作为信号分子来识别胃肠道环境并促进毒力表达。为了成功引起疾病，病原体必须能够感知宿主环境并调节其毒力基因的表达，并与本地微生物群竞争营养。由于肠细胞的更新，乙醇胺 (EA) 存在于大肠中。在这里，我们表明，引起血性腹泻和溶血尿毒症综合征的人类病原体大肠杆菌 O157:H7 通过 EA 代谢和对 EA 作为信号作出反应来调节毒力基因表达。这些发现首次提供了将 EA 与细菌发病机制直接联系起来的信息。
Bacterial pathogens must be able to both recognize suitable niches within the host for colonization and successfully compete with commensal flora for nutrients in order to establish infection. Ethanolamine (EA) is a major component of mammalian and bacterial membranes and is used by pathogens as a carbon and/or nitrogen source in the gastrointestinal tract. The deadly human pathogen enterohemorrhagic Escherichia coli O157:H7 (EHEC) uses EA in the intestine as a nitrogen source as a competitive advantage for colonization over the microbial flora. Here we show that EA is not only important for nitrogen metabolism but that it is also used as a signaling molecule in cell-to-cell signaling to activate virulence gene expression in EHEC. EA in concentrations that cannot promote growth as a nitrogen source can activate expression of EHEC’s repertoire of virulence genes. The EutR transcription factor, known to be the receptor of EA, is only partially responsible for this regulation, suggesting that yet another EA receptor exists. This important link of EA with metabolism, cell-to-cell signaling, and pathogenesis, highlights the fact that a fundamental means of communication within microbial communities relies on energy production and processing of metabolites. Here we show for the first time that bacterial pathogens not only exploit EA as a metabolite but also coopt EA as a signaling molecule to recognize the gastrointestinal environment and promote virulence expression. In order to successfully cause disease, a pathogen must be able to sense a host environment and modulate expression of its virulence genes as well as compete with the indigenous microbiota for nutrients. Ethanolamine (EA) is present in the large intestine due to the turnover of intestinal cells. Here, we show that the human pathogen Escherichia coli O157:H7, which causes bloody diarrhea and hemolytic-uremic syndrome, regulates virulence gene expression through EA metabolism and by responding to EA as a signal. These findings provide the first information directly linking EA with bacterial pathogenesis.