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 of priM, described to encode an antivirulence determinant. By screening a mutant library for increased priM promoter activity, we identified the sensor kinase homolog QseC as an upstream regulator of priM expression, 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 affect priM expression 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 gene priM is modulated by the QseC-PmrA (QseB) TCS in Francisella.

中文翻译：

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传感器激酶QseC调节弗氏杆菌中未连接的PmrA反应调节剂和下游基因表达。

兼性细胞内细菌病原体土拉弗朗西斯菌是人和动物中图拉血病的病原体。革兰氏阴性细菌利用两组分调节系统（TCS）来感知和响应其不断变化的环境。在人类强毒的弗朗西斯菌Tularensis亚种中不存在经典的串联排列的传感器激酶和响应调节剂TCS基因。tularensis，但存在孤儿。PmrA是负责巨噬细胞内生长和毒力的孤儿反应调节剂。然而，对PmrA活性的调节尚不清楚。我们和其他人已经表明，PMRA压制表达PRIM，描述为编码抗毒力决定簇。通过筛选增加priM启动子活性的突变文库，我们确定了传感器激酶同源物QseC为priM表达的上游调节剂，并且该调节部分取决于PmrA（D51）的天冬氨酸磷酸化位点。几种检测到的环境信号，包括肾上腺素，据报道可激活其他细菌中的QseC，但并不以依赖PmrA的方式影响priM的表达。巨噬细胞内存活测定法也质疑PriM是抗毒因子的发现。因此，这些数据表明，PMRA调节的基因PRIM被的QseC-PMRA（QseB）TCS在调制弗朗西斯。