The Sensor Kinase QseC Regulates the Unlinked PmrA Response Regulator and Downstream Gene Expression in Francisella.
The Sensor Kinase QseC Regulates the Unlinked PmrA Response Regulator and Downstream Gene Expression in Francisella.
复制标题
传感器激酶 QseC 调节弗朗西斯菌中未连接的 PmrA 响应调节器和下游基因表达。
DOI：
10.1128/jb.00321-20
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发表时间：
2020
影响因子：
3.2
通讯作者：
Gunn,JohnS
中科院分区：
文献类型：
--
作者：
Hoang,KyVan;Fitch,James;White,Peter;Mohapatra,NrusinghP;Gunn,JohnS
兼性胞内细菌病原体土拉菌弗朗西斯菌是人类和动物土拉菌病的病原体。革兰氏阴性菌利用双组分调节系统（TCS）来感知和响应环境的变化。在人类毒力强的土拉菌亚种中不存在经典的串联排列的感应激酶和反应调节因子TCS基因。图拉伦西斯，但也有孤儿。PmrA是一种孤儿反应调节剂，负责巨噬细胞内生长和毒力；然而，PmrA活性的调控尚不清楚。我们和其他人已经证明PmrA抑制prim的表达，prim被描述为编码抗毒决定因子。通过筛选一个增加引物启动子活性的突变文库，我们确定了传感器激酶同源物QseC是引物表达的上游调节剂，这种调节部分依赖于PmrA的天冬氨酸磷酸化位点（D51）。一些研究的环境信号，包括肾上腺素，据报道在其他细菌中激活QseC，不影响prim表达依赖于PmrA的方式。巨噬细胞内存活测定也质疑PriM是一种抗毒因子的发现。因此，这些数据表明，在francisella中，pmra受QseC-PmrA (QseB) TCS的调控。土拉菌病是由传染性很强的革兰氏阴性病原体土拉菌引起的。这种细菌编码的调节因子很少（例如，双组分系统[TCS]）。PmrA是小鼠模型巨噬细胞存活和毒力所必需的，由一个孤儿TCS反应调节基因编码。目前尚不清楚PmrA是如何响应环境信号来调节基因座的，包括PmrA被抑制的基因。我们发现了一个孤儿传感器激酶（QseC），这是PriM抑制所必需的，并进一步探索了可能调节QseC- pmra TCS和PriM功能的环境信号。
The facultative intracellular bacterial pathogen Francisella tularensis is the causative agent of tularemia in humans and animals. Gram-negative bacteria utilize two-component regulatory systems (TCS) to sense and respond to their changing environment. No classical, tandemly arranged sensor kinase and response regulator TCS genes exist in the human virulent Francisella tularensis subsp.tularensis, but orphaned members are present. PmrA is an orphan response regulator responsible for intramacrophage growth and virulence; however, the regulation of PmrA activity is not understood. We and others have shown that PmrA represses the expression ofpriM, described to encode an antivirulence determinant. By screening a mutant library for increasedpriMpromoter activity, we identified the sensor kinase homolog QseC as an upstream regulator ofpriMexpression, and this regulation is in part dependent upon the aspartate phosphorylation site of PmrA (D51). Several examined environmental signals, including epinephrine, which is reported to activate QseC in other bacteria, do not affectpriMexpression in a manner dependent on PmrA. Intramacrophage survival assays also question the finding that PriM is an antivirulence factor. Thus, these data suggest that the PmrA-regulated genepriMis modulated by the QseC-PmrA (QseB) TCS inFrancisella.IMPORTANCEThe disease tularemia is caused by the highly infectious Gram-negative pathogen Francisella tularensis. This bacterium encodes few regulatory factors (e.g., two-component systems [TCS]). PmrA, required for intramacrophage survival and virulence in the mouse model, is encoded by an orphan TCS response regulator gene. It is unclear how PmrA is responsive to environmental signals to regulate loci, including the PmrA-repressed genepriM. We identify an orphan sensor kinase (QseC) that is required forpriMrepression and further explore both environmental signals that might regulate the QseC-PmrA TCS and the function of PriM.