Magnesium Sensing Regulates Intestinal Colonization of Enterohemorrhagic Escherichia coli O157:H7.
Magnesium Sensing Regulates Intestinal Colonization of Enterohemorrhagic Escherichia coli O157:H7.
复制标题
镁传感调节肠出血性大肠杆菌 O157:H7 的肠道定植
DOI：
10.1128/mbio.02470-20
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发表时间：
2020-11-10
期刊：
影响因子：
6.4
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Liu Y;Han R;Wang J;Yang P;Wang F;Yang B
在肠出血性大肠杆菌（EHEC） O157:H7定植和感染过程中，检测特定的肠道代谢物是诱导关键毒力程序的重要策略。在这里，我们确定了一个毒力调节途径，其中PhoQ/PhoP双组分调控系统向O岛119编码的低镁诱导调节剂a （LmiA）发出信号，LmiA反过来激活肠细胞消除（LEE）基因位点，促进肠出血性大肠杆菌O157:H7在大肠低镁条件下的粘附。这种调节途径广泛存在于一系列肠出血性大肠杆菌和肠致病性大肠杆菌（EPEC）血清型中。这一途径的破坏显著降低了EHEC O157:H7在小鼠肠道中的粘附性。此外，喂食富镁饮食的小鼠体内EHEC O157:H7粘附明显减少，表明镁可能有助于预防人类EHEC和EPEC感染。大肠病原体肠出血性大肠杆菌（EHEC） O157:H7在定植和感染过程中检测宿主信号来调节毒力基因表达。然而，肠出血性大肠杆菌O157:H7在人大肠中的毒力调节机制尚不完全清楚。在此，我们确定了PhoQ/PhoP双组分调控系统感知低镁水平并向O岛119编码的Z4267 （LmiA；低镁诱导调节剂a）发出信号的毒力调控途径，直接激活肠细胞清除基因位点，促进肠出血性大肠杆菌O157:H7粘附在大肠中。这一途径的破坏显著降低了EHEC O157:H7在小鼠肠道中的粘附性。此外，给小鼠喂食富含镁的饮食可显著降低体内EHEC O157:H7粘附。这种由lmia介导的毒力调控途径在几种肠出血性大肠杆菌和肠致病性大肠杆菌血清型中也是保守的；因此，我们的研究结果支持镁作为膳食补充剂的使用，并为预防肠道感染的饮食线索提供了更深入的了解。
Sensing specific gut metabolites is an important strategy for inducing crucial virulence programs by enterohemorrhagic Escherichia coli (EHEC) O157:H7 during colonization and infection. Here, we identified a virulence-regulating pathway wherein the PhoQ/PhoP two-component regulatory system signals to the O island 119-encoded low magnesium-induced regulator A (LmiA), which, in turn, activates locus of enterocyte effacement (LEE) genes to promote EHEC O157:H7 adherence in the low-magnesium conditions of the large intestine. This regulatory pathway is widely present in a range of EHEC and enteropathogenic E. coli (EPEC) serotypes. Disruption of this pathway significantly decreased EHEC O157:H7 adherence in the mouse intestinal tract. Moreover, mice fed a magnesium-rich diet showed significantly reduced EHEC O157:H7 adherence in vivo, indicating that magnesium may help in preventing EHEC and EPEC infection in humans. The large intestinal pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 detects host cues to regulate virulence gene expression during colonization and infection. However, virulence regulatory mechanisms of EHEC O157:H7 in the human large intestine are not fully understood. Herein, we identified a virulence-regulating pathway where the PhoQ/PhoP two-component regulatory system senses low magnesium levels and signals to the O island 119-encoded Z4267 (LmiA; low magnesium-induced regulator A), directly activating loci of enterocyte effacement genes to promote EHEC O157:H7 adherence in the large intestine. Disruption of this pathway significantly decreased EHEC O157:H7 adherence in the mouse intestinal tract. Moreover, feeding mice a magnesium-rich diet significantly reduced EHEC O157:H7 adherence in vivo. This LmiA-mediated virulence regulatory pathway is also conserved among several EHEC and enteropathogenic E. coli serotypes; therefore, our findings support the use of magnesium as a dietary supplement and provide greater insights into the dietary cues that can prevent enteric infections.