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RNA结合蛋白ProQ直接结合并调节肠出血性O157:H7中的毒力基因。

The RNA-binding protein ProQ directly binds and regulates virulence genes in enterohemorrhagic O157:H7.

作者信息

Qian Ye, Zheng Chenguang, Han Runhua

机构信息

School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, China.

School of Public Health, North China University of Science and Technology, Tangshan, China.

出版信息

Front Cell Infect Microbiol. 2025 Aug 29;15:1627518. doi: 10.3389/fcimb.2025.1627518. eCollection 2025.

Abstract

ProQ has recently emerged as a major post-transcriptional regulator in bacteria through directly binding to diverse mRNAs and small regulatory RNAs (sRNAs). However, the impact of ProQ in many pathogenic bacteria remains poorly understood. In this study, we investigated the role of ProQ in enterohaemorrhagic (EHEC), a non-invasive intestinal pathogen. We found that deletion of significantly enhanced cell adherence ability of EHEC and led to upregulation of the locus of enterocyte effacement (LEE) pathogenicity island. This effect was accompanied by reduced expression of genes encoding known LEE regulators, including protein factors ( and ) and sRNAs (GlmY and GlmZ), resulting from decreased stability of their transcripts in the absence of . Additionally, positively regulated bacterial motility by stabilizing mRNA. We further demonstrated that ProQ directly binds to , , / and transcripts at secondary structures located near their 3' ends. Beyond virulence regulation, ProQ also contributed to antibiotic persistence of EHEC and its survival under host-associated stress conditions. Collectively, our findings highlight ProQ as a key gene regulator in EHEC, providing new insights into how this pathogen modulates its virulence at the post-transcriptional level.

摘要

最近,ProQ通过直接结合多种mRNA和小调节RNA(sRNA),成为细菌中一种主要的转录后调节因子。然而,ProQ在许多致病细菌中的作用仍知之甚少。在本研究中,我们调查了ProQ在肠出血性大肠杆菌(EHEC)中的作用,EHEC是一种非侵袭性肠道病原体。我们发现,ProQ的缺失显著增强了EHEC的细胞黏附能力,并导致肠上皮细胞损伤(LEE)致病岛的上调。这种效应伴随着编码已知LEE调节因子的基因表达降低,包括蛋白质因子(和)和sRNA(GlmY和GlmZ),这是由于在没有ProQ的情况下它们转录本的稳定性降低所致。此外,ProQ通过稳定鞭毛蛋白mRNA正向调节细菌的运动性。我们进一步证明,ProQ在位于其3'端附近的二级结构处直接结合鞭毛蛋白、EspA、EspB/EspD和RpoS转录本。除了毒力调节外,ProQ还促进了EHEC的抗生素耐受性及其在宿主相关应激条件下的存活。总的来说,我们的研究结果突出了ProQ作为EHEC中的关键基因调节因子,为这种病原体如何在转录后水平调节其毒力提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/12426089/6c25cb25fda8/fcimb-15-1627518-g001.jpg

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