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通过异源报告系统研究 TcdR 依赖性启动子活性对毒素产生的分子基础。

Molecular Basis of TcdR-Dependent Promoter Activity for Toxin Production by Studied by a Heterologous Reporter System.

机构信息

Key Laboratory of Microbiology and Parasitology of Education Department of Guizhou & Key Laboratory of Medical Molecular Biology of Guizhou Province, Guizhou Medical University, Guiyang 550025, China.

CAS Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Synthetic Biology, Shandong Engineering Laboratory of Single Cell Oil, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China.

出版信息

Toxins (Basel). 2023 Apr 23;15(5):306. doi: 10.3390/toxins15050306.

DOI:10.3390/toxins15050306
PMID:37235341
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10223161/
Abstract

The alternative σ factor TcdR controls the synthesis of two major enterotoxins: TcdA and TcdB in . Four potential TcdR-dependent promoters in the pathogenicity locus of showed different activities. In this study, we constructed a heterologous system in to investigate the molecular basis of TcdR-dependent promoter activity. The promoters of the two major enterotoxins showed strong TcdR-dependent activity, while the two putative TcdR-dependent promoters in the upstream region of the gene did not show detectable activity, suggesting that the autoregulation of TcdR may need other unknown factors involved. Mutation analysis indicated that the divergent -10 region is the key determinant for different activities of the TcdR-dependent promoters. Analysis of the TcdR model predicted by AlphaFold2 suggested that TcdR should be classified into group 4, i.e., extracytoplasmic function, σ factors. The results of this study provide the molecular basis of the TcdR-dependent promoter recognition for toxin production. This study also suggests the feasibility of the heterologous system in analyzing σ factor functions and possibly in drug development targeting these factors.

摘要

TcdR 替代 σ 因子控制. 中两种主要肠毒素 TcdA 和 TcdB 的合成。致病性基因座中存在四个潜在的 TcdR 依赖性启动子，它们具有不同的活性。在这项研究中，我们在. 中构建了一个异源系统，以研究 TcdR 依赖性启动子活性的分子基础。两种主要肠毒素的启动子表现出强烈的 TcdR 依赖性活性，而. 基因上游区域的两个假定的 TcdR 依赖性启动子则没有检测到活性，这表明 TcdR 的自身调控可能需要其他未知的因素参与。突变分析表明，发散的 -10 区是 TcdR 依赖性启动子不同活性的关键决定因素。通过 AlphaFold2 预测的 TcdR 模型分析表明，TcdR 应归类为第四组，即细胞外功能、σ 因子。这项研究为毒素产生的 TcdR 依赖性启动子识别提供了分子基础。本研究还表明，该异源系统在分析 σ 因子功能以及针对这些因子的药物开发方面具有可行性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/08f085ecb7f5/toxins-15-00306-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/d6cebfe984f6/toxins-15-00306-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/e7f4c3174bfd/toxins-15-00306-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/a60718d6027e/toxins-15-00306-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/992a67f79469/toxins-15-00306-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/5a44f9707ea6/toxins-15-00306-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/08f085ecb7f5/toxins-15-00306-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/d6cebfe984f6/toxins-15-00306-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/e7f4c3174bfd/toxins-15-00306-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/a60718d6027e/toxins-15-00306-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/992a67f79469/toxins-15-00306-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/5a44f9707ea6/toxins-15-00306-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4528/10223161/08f085ecb7f5/toxins-15-00306-g006.jpg

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3
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Nat Commun. 2023 Oct 13;14(1):6455. doi: 10.1038/s41467-023-41796-4.
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4
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Nature. 2021 Aug;596(7873):583-589. doi: 10.1038/s41586-021-03819-2. Epub 2021 Jul 15.
5
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