QseBC, a two-component bacterial adrenergic receptor and global regulator of virulence in Enterobacteriaceae and Pasteurellaceae.
QseBC, a two-component bacterial adrenergic receptor and global regulator of virulence in Enterobacteriaceae and Pasteurellaceae.
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DOI：
10.1111/omi.12138
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发表时间：
2016-10
影响因子：
3.7
通讯作者：
Demuth DR
中科院分区：
文献类型：
--
作者：
Weigel WA;Demuth DR
QseBC 双组分系统 (TCS) 与群体感应相关，并作为毒力的全局调节器发挥作用。基于传感器域内的序列相似性和信号识别所必需的酸性基序的保守性，QseBC 主要分布在肠杆菌科和巴氏杆菌科中。在大肠杆菌中，QseC 对自诱导剂 3 和/或肾上腺素/去甲肾上腺素做出反应。肾上腺素/去甲肾上腺素的结合被肾上腺素能拮抗剂抑制；因此，QseC 作为细菌肾上腺素受体发挥作用。伴随放线菌聚集菌 QseC 由肾上腺素/去甲肾上腺素和铁的组合激活，而只有铁才能激活流感嗜血杆菌传感器。 QseC 磷酸化 QseB，但越来越多的证据表明 QseB 被非同源传感器激活，并通过 QseC 的去磷酸化进行调节。有趣的是，QseBC 信号级联和调节子存在显着差异。在肠出血性大肠杆菌中，QseC 诱导第二种肾上腺素 TCS 的表达，并磷酸化两个非同源反应调节因子，每个调节因子都会诱导特定的毒力基因组。该信号通路与转录调节因子 QseA 和 QseD 以及岩藻糖感应 TCS 介导的其他调节机制整合，可能控制毒力基因表达的水平和时间。相比之下，A. actinomycetemcomitans QseC 通过 QseB 发出信号来调节参与厌氧代谢和能量产生的基因，这可能会启动细胞代谢以促进厌氧宿主生态位的生长。 QseC 代表了治疗干预的新靶点，小分子抑制剂已经显示出作为广谱抗菌药物的前景。 QseBC 信号传导的进一步表征可能会识别 QseBC 功能的其他差异，并为进一步开发控制微生物感染的新疗法提供信息。
The QseBC two‐component system (TCS) is associated with quorum sensing and functions as a global regulator of virulence. Based on sequence similarity within the sensor domain and conservation of an acidic motif essential for signal recognition, QseBC is primarily distributed in the Enterobacteriaceae and Pasteurellaceae. In Escherichia coli, QseC responds to autoinducer‐3 and/or epinephrine/norepinephrine. Binding of epinephrine/norepinephrine is inhibited by adrenergic antagonists; hence QseC functions as a bacterial adrenergic receptor. Aggregatibacter actinomycetemcomitans QseC is activated by a combination of epinephrine/norepinephrine and iron, whereas only iron activates the Haemophilus influenzae sensor. QseC phosphorylates QseB but there is growing evidence that QseB is activated by non‐cognate sensors and regulated by dephosphorylation via QseC. Interestingly, the QseBC signaling cascades and regulons differ significantly. In enterohemorrhagic E. coli, QseC induces expression of a second adrenergic TCS and phosphorylates two non‐cognate response regulators, each of which induces specific sets of virulence genes. This signaling pathway integrates with other regulatory mechanisms mediated by transcriptional regulators QseA and QseD and a fucose‐sensing TCS and likely controls the level and timing of virulence gene expression. In contrast, A. actinomycetemcomitans QseC signals through QseB to regulate genes involved in anaerobic metabolism and energy production, which may prime cellular metabolism for growth in an anaerobic host niche. QseC represents a novel target for therapeutic intervention and small molecule inhibitors already show promise as broad‐spectrum antimicrobials. Further characterization of QseBC signaling may identify additional differences in QseBC function and inform further development of new therapeutics to control microbial infections.
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影响因子：
3.2
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通讯作者：
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