Catabolite and Oxygen Regulation of Enterohemorrhagic Escherichia coli Virulence.
Catabolite and Oxygen Regulation of Enterohemorrhagic Escherichia coli Virulence.
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DOI：
10.1128/mbio.01852-16
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发表时间：
2016-11-22
期刊：
影响因子：
6.4
通讯作者：
Sperandio V
中科院分区：
文献类型：
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作者：
Carlson-Banning KM;Sperandio V
肠道的生物地理在其纵轴上以及在特定的微环境中是多样的。不同的氧合和营养成分驱动了这些栖息地中微生物群落的成员。此外，肠道病原体可以协调进一步的修饰，以获得对宿主定殖的竞争优势。这些病原体在利用人类结肠时是多才多艺和熟练的。它们熟练地驾驭复杂的环境线索和王国间的信号来殖民和感染宿主。在这里，我们展示了肠出血性大肠杆菌（EHEC）在暴露于不同氧浓度时如何使用三种糖敏感转录因子，Cra， KdpE和FusR，来精细地调节与其III型分泌系统（T3SS）相关的毒力因子的表达。我们还探讨了黏液来源的非优选碳源对肠出血性大肠杆菌生长和毒力基因表达的影响。综上所述，结果表明，肠出血性大肠杆菌在缺氧时抑制T3SS的表达，模拟大部分无氧的管腔，而在有氧气时通过Cra激活T3SS。此外，当肠出血性大肠杆菌检测到黏液衍生糖大量存在于大肠的o -链和n-链聚糖中时，就会启动毒力基因的表达。果胶是一种复杂的植物多糖，在大肠中被消化，从果胶中提取的糖也增加了毒力基因的表达。肠出血性大肠杆菌不仅感知宿主和微生物群衍生的界间信号，还利用微生物群释放的氧可用性和粘蛋白衍生的糖来刺激T3SS的表达。这种精确的基因调控使得肠出血性大肠杆菌成为一种极低感染剂量的有效病原体。肠道病原体在解释多种环境线索时必须非常狡猾，才能成功地在复杂多样的肠道微环境中建立自己。氧张力和营养成分的差异决定了肠道微生物群的生物地理位置，并提供了肠道病原体可以利用的独特生态位。肠出血性大肠杆菌是一种肠道病原体，在结肠中定植，并在世界范围内引起血性腹泻和溶血性尿毒症综合征的爆发。它的感染剂量非常低，这就要求它是一种非常有效的病原体。因此，本研究表明，肠出血性大肠杆菌可以感知多种糖源和氧水平，以最佳地控制其毒力库的表达。这种精细的调节控制使肠出血性大肠杆菌能够感知不同的肠区室来定植宿主。
The biogeography of the gut is diverse in its longitudinal axis, as well as within specific microenvironments. Differential oxygenation and nutrient composition drive the membership of microbial communities in these habitats. Moreover, enteric pathogens can orchestrate further modifications to gain a competitive advantage toward host colonization. These pathogens are versatile and adept when exploiting the human colon. They expertly navigate complex environmental cues and interkingdom signaling to colonize and infect their hosts. Here we demonstrate how enterohemorrhagic Escherichia coli (EHEC) uses three sugar-sensing transcription factors, Cra, KdpE, and FusR, to exquisitely regulate the expression of virulence factors associated with its type III secretion system (T3SS) when exposed to various oxygen concentrations. We also explored the effect of mucin-derived nonpreferred carbon sources on EHEC growth and expression of virulence genes. Taken together, the results show that EHEC represses the expression of its T3SS when oxygen is absent, mimicking the largely anaerobic lumen, and activates its T3SS when oxygen is available through Cra. In addition, when EHEC senses mucin-derived sugars heavily present in the O-linked and N-linked glycans of the large intestine, virulence gene expression is initiated. Sugars derived from pectin, a complex plant polysaccharide digested in the large intestine, also increased virulence gene expression. Not only does EHEC sense host- and microbiota-derived interkingdom signals, it also uses oxygen availability and mucin-derived sugars liberated by the microbiota to stimulate expression of the T3SS. This precision in gene regulation allows EHEC to be an efficient pathogen with an extremely low infectious dose. Enteric pathogens have to be crafty when interpreting multiple environmental cues to successfully establish themselves within complex and diverse gut microenvironments. Differences in oxygen tension and nutrient composition determine the biogeography of the gut microbiota and provide unique niches that can be exploited by enteric pathogens. EHEC is an enteric pathogen that colonizes the colon and causes outbreaks of bloody diarrhea and hemolytic-uremic syndrome worldwide. It has a very low infectious dose, which requires it to be an extremely effective pathogen. Hence, here we show that EHEC senses multiple sugar sources and oxygen levels to optimally control the expression of its virulence repertoire. This exquisite regulatory control equips EHEC to sense different intestinal compartments to colonize the host.