Indole Sensing Regulator (IsrR) Promotes Virulence Gene Expression in Enteric Pathogens.
Indole Sensing Regulator (IsrR) Promotes Virulence Gene Expression in Enteric Pathogens.
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DOI：
10.1128/mbio.01939-22
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发表时间：
2022-08-30
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;Russell, Regan M.;Hoskan, Mehmet Ali;Sperandio, Vanessa
肠出血性大肠杆菌（EHEC）及其代理小鼠模型鼠柠檬酸杆菌（Citrobacter rodentium）等肠道病原体通过感知肠道内的吲哚水平来导航其生物地理并调节毒力基因表达。吲哚是一种微生物来源的信号，在肠腔中更丰富，其浓度在被吸收的上皮内层降低。大肠杆菌能产生内源性吲哚，因为它含有tnaA基因。微生物来源的外源性吲哚被CpxAR双组分系统感知，其中CpxA是一种膜结合的组氨酸传感器激酶（HK）， CpxR是一种反应调节剂（RR）。吲哚抑制CpxAR功能，导致肠细胞消失（LEE）致病性岛位点的表达降低，这是这些病原体在肠细胞上形成病变所必需的。在我们比较野生型（WT） EHEC和ΔtnaA±吲哚的转录组研究中，吲哚上调最多的基因之一是ygeV，这是一个预测的孤儿RR。由于YgeV在吲哚信号级联中的作用，我们将其重新命名为吲哚感应调节因子（isrR）。在缺乏内源性吲哚的情况下，IsrR激活LEE基因表达。IsrR只对内源性吲哚有反应，外源性吲哚仍然独立于IsrR阻断毒力基因的表达。值得注意的是，啮齿鼠isrR突变体在小鼠感染后被减弱，导致延迟死亡、下肠定植和LEE基因表达。IsrR有助于区分微生物来源（外源性）和内源性自产吲哚，微调肠道病原体的毒力基因表达。
Enteric pathogens such as enterohemorrhagic E. coli (EHEC) and its surrogate murine model Citrobacter rodentium sense indole levels within the gut to navigate its biogeography and modulate virulence gene expression. Indole is a microbiota-derived signal that is more abundant in the intestinal lumen, with its concentration decreasing at the epithelial lining where it is absorbed. E. coli, but not C. rodentium, produces endogenous indole because it harbors the tnaA gene. Microbiota-derived exogenous indole is sensed by the CpxAR two-component system, where CpxA is a membrane-bound histidine-sensor-kinase (HK) and CpxR is a response regulator (RR). Indole inhibits CpxAR function leading to decreased expression of the locus of enterocyte effacement (LEE) pathogenicity island, which is essential for these pathogens to form lesions on enterocytes. In our transcriptome studies comparing wild-type (WT) EHEC and ΔtnaA ± indole, one of the most upregulated genes by indole is ygeV, which is a predicted orphan RR. Because of the role YgeV plays in the indole signaling cascade, we renamed this gene indole sensing regulator (isrR). In the absence of endogenous indole, IsrR activates LEE gene expression. IsrR only responds to endogenous indole, with exogenous indole still blocking virulence gene expression independently from IsrR. Notably, a C. rodentium isrR mutant is attenuated for murine infection, depicting delayed death, lower intestinal colonization, and LEE gene expression. IsrR aids in discriminating between microbiota-derived (exogenous) and endogenous self-produced indole in fine-tuning virulence gene expression by enteric pathogens in the intestine.
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影响因子：
6.4
作者：
Kumar, Aman;Sperandio, Vanessa
通讯作者：
Sperandio, Vanessa
影响因子：
64.5
作者：
Kenny, B;DeVinney, R;Finlay, BB
通讯作者：
Finlay, BB
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL
影响因子：
30.3
作者：
Curtis MM;Hu Z;Klimko C;Narayanan S;Deberardinis R;Sperandio V
通讯作者：
Sperandio V
影响因子：
6.4
作者：
Njoroge JW;Nguyen Y;Curtis MM;Moreira CG;Sperandio V
通讯作者：
Sperandio V