Liu Huizhong, Song Yafeng, Yang Ping, Wang Qian, Huang Ping, Zhang Zhiqing, Zhou Gang, Shi Qingshan, Xie Xiaobao
Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China.
Guangdong Detection Center of Microbiology, Guangzhou 510070, China.
Int J Mol Sci. 2025 Aug 22;26(17):8172. doi: 10.3390/ijms26178172.
Copper ions serve as essential cofactors for many enzymes but exhibit toxicity at elevated concentrations. In Gram-negative bacteria, the Cop system, typically encoded by , plays a crucial role in maintaining copper homeostasis and detoxification. The chromosome of harbors two clusters but lacks , along with two - clusters that encode the cognate two-component system. Here, the roles of these Cop components in countering copper toxicity were studied. We found that was essential for full resistance to Cu in , while made only a minor contribution, partially due to its low expression. The two-component systems CopRS1 and CopRS2 both played significant regulatory roles in copper resistance. Although they could compensate for the absence of each other to mediate copper resistance, they exhibited distinct regulatory effects. CopR1 bound to all four promoters and activated their transcription under copper stress. In contrast, though CopR2 bound to the same sites as CopR1 in each promoter, it significantly activated only and expression. Its competitive binding at the and promoters likely impeded CopR1-mediated activation of these genes. Overall, this study reveals the distinct contributions of the two Cop systems to copper resistance and their regulatory interplay in .
铜离子是许多酶的必需辅因子，但在浓度升高时会表现出毒性。在革兰氏阴性细菌中，通常由[具体基因名称未给出]编码的Cop系统在维持铜稳态和解毒方面起着关键作用。[细菌名称未给出]的染色体含有两个[具体基因簇名称未给出]簇，但缺乏[另一具体基因名称未给出]，以及两个编码同源双组分系统的[具体基因簇名称未给出]簇。在此，研究了这些Cop组分在对抗铜毒性中的作用。我们发现[具体基因名称未给出]对于[细菌名称未给出]对铜的完全抗性至关重要，而[另一具体基因名称未给出]的贡献较小，部分原因是其低表达。双组分系统CopRS1和CopRS2在铜抗性中均发挥重要调节作用。尽管它们可以相互补偿以介导铜抗性，但它们表现出不同的调节作用。CopR1结合到所有四个[具体基因名称未给出]启动子上，并在铜胁迫下激活它们的转录。相比之下，虽然CopR2在每个[具体基因名称未给出]启动子中与CopR1结合在相同位点，但它仅显著激活[具体基因名称未给出]和[另一具体基因名称未给出]的表达。它在[具体基因名称未给出]和[另一具体基因名称未给出]启动子上的竞争性结合可能阻碍了CopR1介导的这些基因的激活。总体而言，本研究揭示了两个Cop系统对铜抗性的不同贡献及其在[细菌名称未给出]中的调节相互作用。
