Indole Signaling at the Host-Microbiota-Pathogen Interface
Indole Signaling at the Host-Microbiota-Pathogen Interface
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DOI：
10.1128/mbio.01031-19
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发表时间：
2019-05-01
期刊：
影响因子：
6.4
通讯作者：
Sperandio, Vanessa
中科院分区：
文献类型：
--
作者：
Kumar, Aman;Sperandio, Vanessa
微生物在胃肠道内的建立需要肠道造影的监测。肠道微生物群通过感知宿主或微生物群衍生的信号来协调行为。在这里，我们第一次表明，微生物来源的吲哚是高度流行的内腔相比，肠组织。吲哚浓度的这种差异在调节肠道病原体肠出血性大肠杆菌（EHEC）和啮齿类柠檬酸杆菌的毒力基因表达中起着关键作用。吲哚降低肠上皮细胞消失（LEE）致病岛基因的表达，这是这些病原体在肠上皮细胞上形成附着和消失（AE）病变所必需的。我们通过使用用抗生素处理的小鼠来消耗微生物群并用产生吲哚的共生多形拟杆菌（B.）重建，综合改变了小鼠胃肠道中吲哚的浓度。θ）或B。theta Delta tnaA突变体（不产生吲哚）或通过工程改造产生吲哚的C.啮齿类菌株这使我们能够评估自产与微生物群产生的吲哚的作用，结果表明，吲哚浓度降低促进细菌致病，而吲哚水平增加降低细菌毒力基因表达。此外，我们确定了细菌膜结合组氨酸传感器激酶（HK）CpxA作为吲哚传感器。肠道病原体感知肠道中吲哚浓度的梯度以探测不同的小生境并成功地建立感染。重要提示病原体感知并响应胃肠道内的几种小分子以调节其毒力谱的表达。吲哚是由肠道微生物群产生的信号分子。在这里，我们表明，吲哚浓度较高的管腔，其中存在的微生物群，比在肠组织。肠道致病菌EHEC和C.啮齿动物感吲哚下调其毒力基因的表达，作为腔室的读出。我们还确定了细菌膜结合的HK CpxA作为吲哚传感器。该法规确保EHEC和C.啮齿类动物只在上皮内层表达它们的毒力基因，这是它们定居的小生境。
Microbial establishment within the gastrointestinal (GI) tract requires surveillance of the gut biogeography. The gut microbiota coordinates behaviors by sensing host-or microbiota-derived signals. Here we show for the first time that microbiota-derived indole is highly prevalent in the lumen compared to the intestinal tissue. This difference in indole concentration plays a key role in modulating virulence gene expression of the enteric pathogens enterohemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium. Indole decreases expression of genes within the locus of enterocyte effacement (LEE) pathogenicity island, which is essential for these pathogens to form attaching and effacing (AE) lesions on enterocytes. We synthetically altered the concentration of indole in the GI tracts of mice by employing mice treated with antibiotics to deplete the microbiota and reconstituted with indole-producing commensal Bacteroides thetaiotaomicron (B. theta) or a B. theta Delta tnaA mutant (does not produce indole) or by engineering an indole-producing C. rodentium strain. This allowed us to assess the role of self-produced versus microbiota-produced indole, and the results show that decreased indole concentrations promote bacterial pathogenesis, while increased levels of indole decrease bacterial virulence gene expression. Moreover, we identified the bacterial membranebound histidine sensor kinase (HK) CpxA as an indole sensor. Enteric pathogens sense a gradient of indole concentrations in the gut to probe different niches and successfully establish an infection.IMPORTANCE Pathogens sense and respond to several small molecules within the GI tract to modulate expression of their virulence repertoire. Indole is a signaling molecule produced by the gut microbiota. Here we show that indole concentrations are higher in the lumen, where the microbiota is present, than in the intestinal tissue. The enteric pathogens EHEC and C. rodentium sense indole to downregulate expression of their virulence genes, as a read-out of the luminal compartment. We also identified the bacterial membrane-bound HK CpxA as an indole sensor. This regulation ensures that EHEC and C. rodentium express their virulence genes only at the epithelial lining, which is the niche they colonize.