A novel small RNA regulates Locus of Enterocyte Effacement and site-specific colonization of enterohemorrhagic Escherichia coli O157:H7 in gut.

IF 4.8 2区医学 Q2 IMMUNOLOGY Frontiers in Cellular and Infection Microbiology Pub Date : 2025-01-15 eCollection Date: 2024-01-01 DOI:10.3389/fcimb.2024.1517328

Runhua Han, Ye Qian, Chenguang Zheng

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Abstract

Enterohemorrhagic Escherichia coli (EHEC) is a contagious foodborne pathogen that specifically colonizes the human large intestine, which is regulated by different environmental stimuli within the gut. Transcriptional regulation of EHEC virulence and infection has been extensively studied, while the posttranscriptional regulation of these processes by small RNAs (sRNAs) remains not fully understood. Here we present a virulence-regulating pathway in EHEC O157:H7, in which the sRNA EvrS binds to and destabilizes the mRNA of Z2269, a novel transcriptional regulator. In turn, Z2269 indirectly activates the expression of LEE (locus of enterocyte effacement) pathogenicity island through the master regulator Ler. Importantly, the expression of EvrS is modulated by environmental oxygen levels. EvrS also exhibits lower expression in the colon compared to the ileum, influencing the site-specific colonization of EHEC O157:H7 in mice. These results indicate that the oxygen status within the intestine may regulate the expression of EvrS, thereby modulating virulence factors of EHEC and contributing to successful infection in vivo. This study has broader implications for understanding sRNA functions in spatiotemporal virulence control of EHEC and may provide novel strategies to prevent EHEC infections.

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一种新的小RNA调节肠出血性大肠杆菌O157:H7在肠道中的肠细胞消失位点和特异性定植。

肠出血性大肠杆菌（EHEC）是一种传染性食源性病原体，其特异性定植于人类大肠，受肠道内不同环境刺激的调节。肠出血性大肠杆菌毒力和感染的转录调控已被广泛研究，而小rna （sRNAs）对这些过程的转录后调控仍未完全了解。在这里，我们提出了EHEC O157:H7的毒力调节途径，其中sRNA EvrS结合并破坏Z2269的mRNA， Z2269是一种新的转录调节剂。反过来，Z2269通过主调控因子Ler间接激活LEE （enterocyte effement locus of enterocyte effement）致病性岛的表达。重要的是，evr的表达受环境氧水平的调节。与回肠相比，EvrS在结肠中的表达也较低，这影响了小鼠肠出血性大肠杆菌O157:H7的定点定植。这些结果表明，肠道内的氧状态可能调节EvrS的表达，从而调节肠出血性大肠杆菌的毒力因子，并有助于体内感染的成功。该研究对理解sRNA在肠出血性大肠杆菌时空毒力控制中的功能具有更广泛的意义，并可能为预防肠出血性大肠杆菌感染提供新的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Cellular and Infection Microbiology IMMUNOLOGY-MICROBIOLOGY

CiteScore

7.90

自引率

7.00%

发文量

1817

审稿时长

14 weeks

期刊介绍： Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.