Xu Chenchen, Cao Qiao, Lan Lefu
University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Microorganisms. 2021 Feb 21;9(2):447. doi: 10.3390/microorganisms9020447.
A two-component system GtrS-GltR is required for glucose transport activity in and plays a key role during -host interactions. However, the mechanism of action of GtrS-GltR has not been definitively established. Here, we show that , which encodes a periplasmic glucose binding protein, is essential for the glucose-induced activation of GtrS-GltR in . We determined that GltB is capable of binding to membrane regulatory proteins including GtrS, the sensor kinase of the GtrS-GltR TCS. We observed that alanine substitution of glucose-binding residues abolishes the ability of GltB to promote the activation of GtrS-GltR. Importantly, like the deletion mutant, deletion mutant showed attenuated virulence in both and mouse models of infection. In addition, using CHIP-seq experiments, we showed that the promoter of is the major in vivo target of GltR. Collectively, these data suggest that periplasmic binding protein GltB and GtrS-GltR TCS form a complex regulatory circuit that regulates the virulence of in response to glucose.
双组分系统GtrS - GltR对于[具体细菌名称]中的葡萄糖转运活性是必需的，并且在[细菌名称]与宿主相互作用过程中起关键作用。然而，GtrS - GltR的作用机制尚未明确确立。在此，我们表明，编码周质葡萄糖结合蛋白的[具体基因名称]对于[具体细菌名称]中葡萄糖诱导的GtrS - GltR激活至关重要。我们确定GltB能够与包括GtrS（GtrS - GltR双组分系统的传感激酶）在内的膜调节蛋白结合。我们观察到葡萄糖结合残基的丙氨酸替代消除了GltB促进GtrS - GltR激活的能力。重要的是，与[具体基因名称]缺失突变体一样，[具体基因名称]缺失突变体在[具体细菌名称]感染的[具体动物名称]和小鼠模型中均表现出毒力减弱。此外，使用染色质免疫沉淀测序（CHIP - seq）实验，我们表明[具体基因名称]的启动子是GltR在体内的主要靶标。总体而言，这些数据表明周质结合蛋白GltB和GtrS - GltR双组分系统形成了一个复杂的调节回路，该回路响应葡萄糖调节[具体细菌名称]的毒力。
