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Differential modulation of flagella expression in enterohaemorrhagic Escherichia coli O157:?H7 by intestinal short-chain fatty acid mixes

机译:肠道短链脂肪酸混合物对肠出血性大肠杆菌O157:?H7中鞭毛表达的差异调节

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During passage through the gastrointestinal tract, enterohaemorrhagic Escherichia coli (EHEC) encounters numerous stresses, each producing unique antimicrobial conditions. Beyond surviving these stresses, EHEC may also use them as cues about the local microenvironment to modulate its virulence. Of particular interest is how exposure to changing concentrations of short-chain fatty acids (SCFAs) associated with passage through the small and large intestines affects EHEC virulence, as well as flagella expression and motility specifically. In this study, we investigate the impact of exposure to SCFA mixes simulating concentrations and compositions within the small and large intestines on EHEC flagella expression and function. Using a combination of DNA microarray, quantitative real-time PCR, immunoblot analysis, flow cytometry and motility assays, we show that there is a marked, significant upregulation of flagellar genes, the flagellar protein, FliC, and motility when EHEC is exposed to SCFA mixes representative of the small intestine. By contrast, when EHEC is exposed to SCFA mixes representative of the large intestine, there is a significant downregulation of flagellar genes, FliC and motility. Our results demonstrate that EHEC modulates flagella expression and motility in response to SCFAs, with differential responses associated with SCFA mixes typical of the small and large intestines. This research contributes to our understanding of how EHEC senses and responds to host environmental signals and the mechanisms it uses to successfully infect the human host. Significantly, it also suggests that EHEC is using this key gastrointestinal chemical signpost to cue changes in flagella expression and motility in different locations within the host intestinal tract.
机译:在通过胃肠道的过程中,肠出血性大肠杆菌(EHEC)会遇到许多压力,每种压力都会产生独特的抗菌状况。除了克服这些压力外,EHEC还可以将它们用作有关局部微环境的线索以调节其毒性。特别令人感兴趣的是,暴露于与通过小肠和大肠有关的短链脂肪酸(SCFA)浓度变化如何特别影响EHEC毒力以及鞭毛表达和运动能力。在这项研究中,我们调查了模拟小肠和大肠中浓度和成分对SCFA混合物的暴露对EHEC鞭毛表达和功能的影响。通过结合使用DNA芯片,实时荧光定量PCR,免疫印迹分析,流式细胞仪和活力测定,我们发现当EHEC暴露于SCFA时,鞭毛基因,鞭毛蛋白,FliC和活力明显显着上调混合代表小肠。相比之下,当EHEC暴露于代表大肠的SCFA混合物时,鞭毛基因,FliC和运动性显着下调。我们的结果表明,EHEC调节鞭毛表达和运动能力以响应SCFA,并具有与小肠和大肠典型的SCFA混合物相关的不同应答。这项研究有助于我们了解EHEC如何感测和响应宿主环境信号及其成功感染人类宿主的机制。重要的是,这也表明EHEC正在利用这一关键的胃肠道化学路标来提示宿主肠道内不同位置的鞭毛表达和运动能力的变化。

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