Liu Yutao, Li Shujie, Li Wendi, Wang Peisheng, Ding Peng, Li Lingyu, Wang Junyue, Yang Pan, Wang Qian, Xu Tingting, Xiong Yingying, Yang Bin
1The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin, 300071 People's Republic of China.
TEDA, Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin, 300457 People's Republic of China.
Gut Pathog. 2019 Nov 1;11:53. doi: 10.1186/s13099-019-0335-4. eCollection 2019.
Enterohemorrhagic O157:H7 (EHEC O157) causes bloody diarrhea and hemolytic-uremic syndrome. EHEC O157 encounters varied microenvironments during infection, and can efficiently adapt to these using the two-component system (TCS). Recently, a functional TCS, RstAB, has been implicated in the regulation of virulence of several bacterial pathogens. However, the regulatory function of RstAB in EHEC O157 is poorly understood. This study aimed at providing insights into the global effects of RstA on gene expression in EHEC O157.
In the present study, we analyzed gene expression differences between the EHEC O157 wild-type strain and a Δ mutant using RNA-seq technology. Genes with differential expression in the Δ mutant compared to that in the wild-type strain were identified and grouped into clusters of orthologous categories. RstA promoted EHEC O157 LEE gene expression, adhesion in vitro, and colonization in vivo by indirect regulation. We also found that RstA could bind directly to the promoter region of and to enhance acid tolerance and decrease biofilm formation by modulating the concentration of c-di-GMP.
In summary, the RstAB TCS in EHEC O157 plays a major role in the regulation of virulence, acid tolerance, and biofilm formation. We clarified the regulatory function of RstA, providing an insight into mechanisms that may be potential drug targets for treatment of EHEC O157-related infections.
肠出血性O157:H7（EHEC O157）可引起血性腹泻和溶血尿毒综合征。EHEC O157在感染过程中会遇到多种微环境，并可利用双组分系统（TCS）有效地适应这些环境。最近，一种功能性TCS，即RstAB，已被证明与几种细菌病原体的毒力调节有关。然而，RstAB在EHEC O157中的调节功能尚不清楚。本研究旨在深入了解RstA对EHEC O157基因表达的全局影响。
在本研究中，我们使用RNA测序技术分析了EHEC O157野生型菌株和Δ突变体之间的基因表达差异。确定了与野生型菌株相比在Δ突变体中差异表达的基因，并将其归类为直系同源类别簇。RstA通过间接调节促进EHEC O157的LEE基因表达、体外黏附和体内定植。我们还发现，RstA可以直接结合和的启动子区域，通过调节环二鸟苷酸（c-di-GMP）的浓度来增强耐酸性并减少生物膜形成。
总之，EHEC O157中的RstAB TCS在毒力、耐酸性和生物膜形成的调节中起主要作用。我们阐明了RstA的调节功能，为可能成为治疗EHEC O157相关感染的潜在药物靶点的机制提供了见解。
