Department of Microbiology, College of Life Sciences, Nankai Universitygrid.216938.7, Tianjin, China.
Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin, China.
Microbiol Spectr. 2022 Aug 31;10(4):e0154322. doi: 10.1128/spectrum.01543-22. Epub 2022 Jul 7.
Nucleoside transport is essential for maintaining intracellular nucleoside and nucleobase homeostasis for living cells. Here, we identified an uncharacterized GntR/HutC family transcriptional regulator, NagR2, renamed NupR (nucleoside permease regulator), that mainly controls nucleoside transport in the Bacillus thuringiensis BMB171 strain. The deletion or overexpression of affected the bacteria's utilization of guanosine, adenosine, uridine, and cytidine rather than thymidine. We further demonstrated that zinc ion is an effector for the NupR, dissociating NupR from its target DNA. Moreover, the expression of is inhibited by NupR, ComK, and PurR, while it is promoted by CcpA. Also, a purine riboswitch located in its 5' noncoding region influences the expression of . Guanine is the ligand of the riboswitch, reducing the expression of by terminating the transcription of in advance. Hence, our results reveal an exquisite regulation mechanism enabling NupR to respond to multiple signals, control genes involved in nucleoside transport, and contribute to nucleoside substance utilization. Overall, this study provides essential clues for future studies exploring the function of the NupR homolog in other bacteria, such as Bacillus cereus, Bacillus anthracis, Klebsiella pneumoniae, and Streptococcus pneumoniae. The transport of nucleosides and their homeostasis within the cell are essential for growth and proliferation. Here, we have identified a novel transcription factor, NupR, which, to our knowledge, is the first GntR family transcription factor primarily involved in the regulation of nucleoside transport. Moreover, responding to diverse intracellular signals, NupR regulates nucleoside transport. It is vital for utilizing extracellular nucleosides and maintaining intracellular nucleoside homeostasis. NupR may also be involved in other pathways such as pH homeostasis, molybdenum cofactor biosynthesis, nitrate metabolism, and transport. In addition, nucleosides have various applications, such as antiviral drugs. Thus, the elucidation of the transport mechanism of nucleosides could be helpful for the construction of engineered strains for nucleoside production.
核苷转运对于维持细胞内核苷和碱基的内环境稳定至关重要。在这里，我们鉴定了一个未被描述的 GntR/HutC 家族转录调节因子，NagR2，将其重新命名为 NupR（核苷渗透调节因子），它主要控制苏云金芽孢杆菌 BMB171 菌株中的核苷转运。的缺失或过表达影响了细菌对鸟苷、腺苷、尿苷和胞苷的利用，而不是胸苷。我们进一步证明锌离子是 NupR 的效应物，使 NupR 与靶 DNA 解离。此外，NupR、ComK 和 PurR 抑制的表达，而 CcpA 则促进其表达。此外，位于其 5'非编码区的嘌呤核糖开关影响的表达。鸟嘌呤是核糖开关的配体，通过提前终止的转录来降低的表达。因此，我们的结果揭示了一种精细的调控机制，使 NupR 能够对多种信号做出反应，控制参与核苷转运的基因，并有助于核苷物质的利用。总的来说，这项研究为未来研究 NupR 同源物在其他细菌（如蜡状芽孢杆菌、炭疽芽孢杆菌、肺炎克雷伯菌和肺炎链球菌）中的功能提供了重要线索。核苷及其在细胞内的稳态运输对于生长和增殖至关重要。在这里，我们鉴定了一种新的转录因子 NupR，据我们所知，这是第一个主要参与核苷转运调控的 GntR 家族转录因子。此外，NupR 响应多种细胞内信号，调节核苷转运。它对于利用细胞外核苷和维持细胞内核苷稳态至关重要。NupR 可能还参与其他途径，如 pH 稳态、钼辅因子生物合成、硝酸盐代谢和运输。此外，核苷具有多种应用，如抗病毒药物。因此，阐明核苷的转运机制可能有助于构建用于核苷生产的工程菌株。
