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, SAR, China.
BMC Microbiol. 2024 Nov 29;24(1):509. doi: 10.1186/s12866-024-03671-0.
Pseudomonas aeruginosa is able to survive, grow, and cause severe infections at different sites throughout the human body owing to its ability to sense diverse signals and precisely modulate target gene expression using its abundant signaling systems. Release of zinc (Zn) and hydrogen peroxide (HO) within the phagocyte are two major host strategies to defend against bacterial infections. It was previously shown that the response regulator CzcR controls global gene expression including catalase genes during Zn excess, but regulatory mechanisms of catalase gene expression and the role of CzcR in HO tolerance remain unclear.
In the study, comparative transcriptome analysis comprehensively described the CzcR-dependent and -independent gene regulatory pattern in P. aeruginosa during Zn excess, which revealed the counteractive co-regulation of two key HO-detoxifying catalase genes katA and katB through CzcR-dependent and -independent pathways in response to Zn excess. Protein-DNA interaction assay demonstrated that CzcR negatively regulates the expression of catalase genes katA and katB by directly binding to their promoters. While interestingly, we further showed that CzcR positively regulates HO tolerance by inducing the catalase activity during Zn excess.
This study reported the opposite functions of CzcR in negatively regulating the expression of catalase genes katA and katB but in positively regulating the activity of catalase and HO tolerance during Zn excess in P. aeruginosa.
铜绿假单胞菌能够在人体的不同部位生存、生长并引起严重感染,这要归功于其感知各种信号的能力,以及使用其丰富的信号系统精确调节靶基因表达的能力。吞噬细胞内锌(Zn)和过氧化氢(HO)的释放是宿主抵抗细菌感染的两种主要策略。先前的研究表明,响应调节剂 CzcR 在 Zn 过剩时控制包括过氧化氢酶基因在内的全局基因表达,但过氧化氢酶基因表达的调控机制和 CzcR 在 HO 耐受中的作用仍不清楚。
在这项研究中,比较转录组分析全面描述了 Zn 过剩时铜绿假单胞菌中 CzcR 依赖性和非依赖性基因调控模式,揭示了通过 CzcR 依赖性和非依赖性途径,在 Zn 过剩时对两种关键 HO 解毒过氧化氢酶基因 katA 和 katB 进行拮抗的共调控。蛋白-DNA 相互作用实验表明,CzcR 通过直接结合其启动子,负调控过氧化氢酶基因 katA 和 katB 的表达。有趣的是,我们进一步表明,CzcR 通过在 Zn 过剩时诱导过氧化氢酶活性,正向调节 HO 耐受。
本研究报告了 CzcR 在负调控过氧化氢酶基因 katA 和 katB 的表达方面的相反功能,但在 Zn 过剩时正调控铜绿假单胞菌中过氧化氢酶的活性和 HO 耐受。