Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou, China.
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Appl Environ Microbiol. 2024 Mar 20;90(3):e0232723. doi: 10.1128/aem.02327-23. Epub 2024 Feb 20.
Zinc is an important transition metal that is essential for numerous physiological processes while excessive zinc is cytotoxic. is a ubiquitous opportunistic human pathogen equipped with an exquisite zinc homeostatic system, and the two-component system CzcS/CzcR plays a key role in zinc detoxification. Although an increasing number of studies have shown the versatility of CzcS/CzcR, its physiological functions are still not fully understood. In this study, transcriptome analysis was performed, which revealed that CzcS/CzcR is silenced in the absence of the zinc signal but modulates global gene expression when the pathogen encounters zinc excess. CzcR was demonstrated to positively regulate the copper tolerance gene and negatively regulate the pyochelin biosynthesis regulatory gene through direct binding to their promoters. Remarkably, the upregulation of and downregulation of were shown to rescue the impaired capacity of copper tolerance and prevent pyochelin overproduction, respectively, caused by zinc excess. This study not only advances our understanding of the regulatory spectrum of CzcS/CzcR but also provides new insights into stress adaptation mediated by two-component systems in bacteria to balance the cellular processes that are disturbed by their signals.
CzcS/CzcR is a two-component system that has been found to modulate zinc homeostasis, quorum sensing, and antibiotic resistance in . To fully understand the physiological functions of CzcS/CzcR, we performed a comparative transcriptome analysis in this study and discovered that CzcS/CzcR controls global gene expression when it is activated during zinc excess. In particular, we demonstrated that CzcS/CzcR is critical for maintaining copper tolerance and iron homeostasis, which are disrupted during zinc excess, by inducing the expression of the copper tolerance gene and repressing the pyochelin biosynthesis genes through . This study revealed the global regulatory functions of CzcS/CzcR and described a new and intricate adaptive mechanism in response to zinc excess in . The findings of this study have important implications for novel anti-infective interventions by incorporating metal-based drugs.
锌是一种重要的过渡金属，对于许多生理过程都是必不可少的，而过量的锌则具有细胞毒性。是一种普遍存在的机会主义人类病原体，拥有精致的锌稳态系统，而双组分系统 CzcS/CzcR 在锌解毒中起着关键作用。尽管越来越多的研究表明了 CzcS/CzcR 的多功能性，但它的生理功能仍未完全理解。在这项研究中，进行了转录组分析，结果表明，当病原体遇到锌过量时，CzcS/CzcR 在没有锌信号的情况下被沉默，但会调节全局基因表达。CzcR 被证明通过直接结合它们的启动子，正向调节铜耐受基因 和负向调节吡咯啉生物合成调节基因 。值得注意的是， 上调和 下调分别显示出可挽救由锌过量引起的铜耐受能力受损和防止吡咯啉过度产生。这项研究不仅推进了我们对 CzcS/CzcR 调控谱的理解，还为细菌中双组分系统介导的应激适应提供了新的见解，以平衡其信号扰乱的细胞过程。
CzcS/CzcR 是一种双组分系统，已被发现可调节 中的锌稳态、群体感应和抗生素耐药性。为了全面了解 CzcS/CzcR 的生理功能，我们在这项研究中进行了比较转录组分析，发现当锌过量时激活 CzcS/CzcR 会控制全局基因表达。特别是，我们证明 CzcS/CzcR 通过诱导铜耐受基因 的表达和通过 抑制吡咯啉生物合成基因的表达，对于在锌过量时维持铜耐受和铁稳态至关重要，而这些过程在锌过量时会受到干扰。这项研究揭示了 CzcS/CzcR 的全局调控功能，并描述了一种针对锌过量的新的、复杂的适应机制。这项研究的发现对于通过整合金属基药物进行新型抗感染干预具有重要意义。
