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岛 9 编码的 LysR 型转录调节子 OvrB 驱动肠出血性 O157:H7 毒力。

LysR-type transcriptional regulator OvrB encoded in O island 9 drives enterohemorrhagic O157:H7 virulence.

机构信息

TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA , Tianjin , P. R. China.

The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education , Tianjin , P. R. China.

出版信息

Virulence. 2019 Dec;10(1):783-792. doi: 10.1080/21505594.2019.1661721.

DOI:10.1080/21505594.2019.1661721
PMID:31502495
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6768210/
Abstract

Enterohemorrhagic (EHEC) O157:H7 (O157) is a major foodborne pathogen that causes severe illness in humans worldwide. The genome of O157 contains 177 genomic islands known as O islands (OIs), including Shiga toxin-converting phages (OI-45 and OI-93) and the locus for enterocyte effacement (LEE) pathogenicity island (OI-148). However, most genes in OIs are uncharacterized and code for unknown functions. In this study, we demonstrated, for the first time, that OI-9 encodes a novel transcriptional activator, Z0346 (named OvrB), which is required for bacterial adherence to host cells and LEE gene expression in O157. OvrB directly binds to the promoter region of LEE1 and activates the transcription of ler (encoding a master regulator of LEE genes), which in turn activates LEE1-5 genes to promote O157 adherence. Furthermore, mouse oral infection assays showed that OvrB promotes O157 colonization in the mouse intestine. Finally, OvrB is shown to be a widespread transcriptional activator of virulence genes in other enterohemorrhagic and enteropathogenic serotypes. Our work significantly expands the understanding of bacterial virulence control and provides new evidence suggesting that horizontally transferred regulator genes mediate LEE gene expression.

摘要

肠出血性大肠杆菌（EHEC）O157：H7（O157）是一种主要的食源性病原体，在全球范围内导致人类严重疾病。O157 的基因组包含 177 个称为 O 岛（OIs）的基因组岛，包括志贺毒素转化噬菌体（OI-45 和 OI-93）和肠细胞消失（LEE）致病性岛（OI-148）。然而，大多数 OIs 中的基因尚未被描述，其编码未知功能。在这项研究中，我们首次证明 OI-9 编码一种新型转录激活子 Z0346（命名为 OvrB），它是 O157 细菌与宿主细胞粘附和 LEE 基因表达所必需的。OvrB 直接结合 LEE1 的启动子区域并激活 ler（编码 LEE 基因的主调控因子）的转录，进而激活 LEE1-5 基因以促进 O157 粘附。此外，小鼠口服感染实验表明，OvrB 促进 O157 在小鼠肠道中的定植。最后，OvrB 被证明是其他肠出血性和肠致病性血清型中广泛的毒力基因转录激活子。我们的工作极大地扩展了对细菌毒力控制的理解，并提供了新的证据表明，水平转移的调节基因介导 LEE 基因表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/7f8cbeab2278/kvir-10-01-1661721-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/e08bf62a8b82/kvir-10-01-1661721-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/98eeac6172cf/kvir-10-01-1661721-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/892b89e7b5a6/kvir-10-01-1661721-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/471c12f24e47/kvir-10-01-1661721-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/0c341f2fc5ce/kvir-10-01-1661721-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/7f8cbeab2278/kvir-10-01-1661721-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/e08bf62a8b82/kvir-10-01-1661721-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/98eeac6172cf/kvir-10-01-1661721-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/892b89e7b5a6/kvir-10-01-1661721-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/471c12f24e47/kvir-10-01-1661721-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/0c341f2fc5ce/kvir-10-01-1661721-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/044e/6768210/7f8cbeab2278/kvir-10-01-1661721-g006.jpg

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本文引用的文献

[1]
Transcriptional Activator GmrA, Encoded in Genomic Island OI-29, Controls the Motility of Enterohemorrhagic O157:H7.

Front Microbiol. 2018-2-22

[2]
Signal transduction pathway mediated by the novel regulator LoiA for low oxygen tension induced Salmonella Typhimurium invasion.

PLoS Pathog. 2017-6-2

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Crit Rev Eukaryot Gene Expr. 2015

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Enterohemorrhagic Escherichia coli senses low biotin status in the large intestine for colonization and infection.

Nat Commun. 2015-3-20

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PLoS One. 2013-6-13

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Front Cell Infect Microbiol. 2013-4-30

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Molecular evolution of LysR-type transcriptional regulation in Pseudomonas aeruginosa.

Mol Phylogenet Evol. 2012-12-27

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Novel repressor of Escherichia coli O157:H7 motility encoded in the putative fimbrial cluster OI-1.

J Bacteriol. 2012-7-27

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