RNA-seq reveals the critical role of Lon protease in stress response and Brucella virulence
RNA-seq reveals the critical role of Lon protease in stress response and Brucella virulence
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RNA-seq揭示了Lon蛋白酶在应激反应和布鲁氏菌毒力中的关键作用
DOI：
10.1016/j.micpath.2019.01.010
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发表时间：
2019-05-01
影响因子：
3.8
通讯作者：
Chen, Ruiai
中科院分区：
文献类型：
--
作者：
Liu, Yufu;Dong, Hao;Chen, Ruiai
布鲁氏菌在其宿主细胞内遇到应激环境。Lon蛋白是布鲁氏菌中一种重要的蛋白酶，与细胞蛋白质降解和抗逆性有关。然而，Lon蛋白与胁迫反应之间的分子机制尚不清楚。研究发现，离子突变株在TSB培养基中的生长缺陷较亲本菌株明显。此外，我们的研究结果表明，Lon蛋白参与了对各种胁迫条件和所有测试的β-内酰胺抗生素的抗性。虽然该蛋白酶的缺失不影响布鲁氏菌在巨噬细胞中的毒力，但突变株在小鼠感染模型中在感染后1周显著减毒，并且体内几种细胞因子基因的表达水平显著改变。为了深入了解离子突变株所表现出的独特表型特性的遗传基础，进行了RNA-seq，结果表明，在Delta lon菌株中，参与胁迫反应、群体感应和转录调控的各种基因发生了显著改变。这些研究初步揭示了Lon蛋白酶、胁迫反应和细菌毒力之间的分子机制。
The Brucella spp encounter stressful environment inside their host cells. The Lon protein is an important protease related to cellular protein degradation and resistance to stress in Brucelia. However, the molecular mechanism between Lon protein and stress response was still unknown. In this study, it was found that the ion mutant exhibited obvious growth defect in TSB medium, compared with its parent strain. In addition, our results indicated that Lon protein was involved in resistance to various stress conditions and all the beta-lactam antibiotics tested. Although deletion of this protease did not affect Brucella virulence in macrophage, the mutant strain was significantly attenuated in mice infection model at 1 week post infection, and the expression level of several cytokine genes was significantly changed in vivo. To gain insight into the genetic basis for the distinctive phenotypic properties exhibited by the ion mutant strain, RNA-seq was performed, and the result showed that various genes involved in stress response, quorum sensing and transcriptional regulation were significantly altered in Delta lon strain. Overall, these studies have preliminary uncovered the molecular mechanism between Lon protease, stress response and bacterial virulence.