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艰难梭菌毒力因子的表型变异。

Phase variation of Clostridium difficile virulence factors.

机构信息

a Department of Microbiology and Immunology , University of North Carolina at Chapel Hill , Chapel Hill , NC , USA.

出版信息

Gut Microbes. 2018 Jan 2;9(1):76-83. doi: 10.1080/19490976.2017.1362526. Epub 2017 Sep 21.

DOI:10.1080/19490976.2017.1362526
PMID:28806147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5914908/
Abstract

Clostridium difficile is a leading cause of nosocomial infections, causing disease that ranges from mild diarrhea to potentially fatal colitis. A variety of surface proteins, including flagella, enable C. difficile colonization of the intestine. Once in the intestine, toxigenic C. difficile secretes two glucosylating toxins, TcdA and TcdB, which elicit inflammation and diarrheal disease symptoms. Regulation of colonization factors and TcdA and TcdB is an intense area of research in C. difficile biology. A recent publication from our group describes a novel regulatory mechanism that mediates the ON/OFF expression of co-regulated virulence factors of C. difficile, flagella and toxins. Herein, we review key findings from our work, present new data, and speculate the functional consequence of the ON/OFF expression of these virulence factors during host infection.

摘要

艰难梭菌是医院获得性感染的主要原因,可引起从轻度腹泻到潜在致命性结肠炎等多种疾病。多种表面蛋白,包括鞭毛,使艰难梭菌能够在肠道中定植。一旦进入肠道,产毒艰难梭菌就会分泌两种葡糖基化毒素,TcdA 和 TcdB,引发炎症和腹泻症状。定植因子以及 TcdA 和 TcdB 的调控是艰难梭菌生物学研究的一个热点领域。我们小组最近的一篇论文描述了一种新的调控机制,介导艰难梭菌共同调控的毒力因子——鞭毛和毒素的开/关表达。本文中,我们将回顾我们工作中的关键发现,呈现新的数据,并推测这些毒力因子在宿主感染过程中的开/关表达的功能后果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/5914908/02ac27f5e936/kgmi-09-01-1362526-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/5914908/c7912c5384c3/kgmi-09-01-1362526-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/5914908/02ac27f5e936/kgmi-09-01-1362526-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/5914908/c7912c5384c3/kgmi-09-01-1362526-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/5914908/02ac27f5e936/kgmi-09-01-1362526-g002.jpg

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本文引用的文献

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Clostridium difficile flagella induce a pro-inflammatory response in intestinal epithelium of mice in cooperation with toxins.艰难梭菌鞭毛与毒素协同诱导小鼠肠道上皮产生促炎反应。
Sci Rep. 2017 Jun 12;7(1):3256. doi: 10.1038/s41598-017-03621-z.
2
A genetic switch controls the production of flagella and toxins in Clostridium difficile.一种基因开关控制着艰难梭菌中鞭毛和毒素的产生。
PLoS Genet. 2017 Mar 27;13(3):e1006701. doi: 10.1371/journal.pgen.1006701. eCollection 2017 Mar.
3
A Clostridium difficile Cell Wall Glycopolymer Locus Influences Bacterial Shape, Polysaccharide Production and Virulence.
单细胞延时显微镜揭示的5型艰难梭菌菌株独特的生长和形态特性
PLoS Pathog. 2025 May 21;21(5):e1013155. doi: 10.1371/journal.ppat.1013155.
4
Flagella.鞭毛。
Int J Mol Sci. 2024 Feb 12;25(4):2202. doi: 10.3390/ijms25042202.
5
Phase Variation of Flagella and Toxins in Clostridioides difficile is Mediated by Selective Rho-dependent Termination.艰难梭菌中鞭毛和毒素的相变由选择性的 Rho 依赖性终止介导。
J Mol Biol. 2024 Mar 15;436(6):168456. doi: 10.1016/j.jmb.2024.168456. Epub 2024 Jan 24.
6
Role of the Alteration in Calcium Homeostasis in Cell Death Induced by Toxin A and Toxin B.钙稳态改变在毒素A和毒素B诱导的细胞死亡中的作用
Biology (Basel). 2023 Aug 10;12(8):1117. doi: 10.3390/biology12081117.
7
The interactions of Candida albicans with gut bacteria: a new strategy to prevent and treat invasive intestinal candidiasis.白色念珠菌与肠道细菌的相互作用:预防和治疗侵袭性肠道念珠菌病的新策略。
Gut Pathog. 2023 Jun 27;15(1):30. doi: 10.1186/s13099-023-00559-8.
8
Effects of Omeprazole on Recurrent Clostridioides difficile Infection Caused by ST81 Strains and Their Potential Mechanisms.奥美拉唑对 ST81 型菌株引起的复发性艰难梭菌感染的影响及其潜在机制。
Antimicrob Agents Chemother. 2023 Jun 15;67(6):e0022123. doi: 10.1128/aac.00221-23. Epub 2023 May 24.
9
Host Sorbitol and Bacterial Sorbitol Utilization Promote Clostridioides difficile Infection in Inflammatory Bowel Disease.宿主山梨糖醇和细菌山梨糖醇利用促进炎症性肠病中的艰难梭菌感染。
Gastroenterology. 2023 Jun;164(7):1189-1201.e13. doi: 10.1053/j.gastro.2023.02.046. Epub 2023 Mar 8.
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Cytotoxic synergism of toxin B with proinflammatory cytokines in subjects with inflammatory bowel diseases.炎症性肠病患者中毒素 B 与促炎细胞因子的细胞毒性协同作用。
World J Gastroenterol. 2023 Jan 28;29(4):582-596. doi: 10.3748/wjg.v29.i4.582.
艰难梭菌细胞壁糖聚合物基因座影响细菌形态、多糖产生及毒力。
PLoS Pathog. 2016 Oct 14;12(10):e1005946. doi: 10.1371/journal.ppat.1005946. eCollection 2016 Oct.
4
What's a SNP between friends: The influence of single nucleotide polymorphisms on virulence and phenotypes of Clostridium difficile strain 630 and derivatives.朋友之间有什么 SNP:单核苷酸多态性对艰难梭菌 630 株及其衍生物毒力和表型的影响。
Virulence. 2017 Aug 18;8(6):767-781. doi: 10.1080/21505594.2016.1237333. Epub 2016 Sep 21.
5
Cyclic diguanylate signaling in Gram-positive bacteria.革兰氏阳性菌中的环二鸟苷酸信号传导
FEMS Microbiol Rev. 2016 Sep;40(5):753-73. doi: 10.1093/femsre/fuw013. Epub 2016 Jun 26.
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Clostridium difficile flagella predominantly activate TLR5-linked NF-κB pathway in epithelial cells.艰难梭菌鞭毛主要激活上皮细胞中与Toll样受体5(TLR5)相关的核因子κB(NF-κB)信号通路。
Anaerobe. 2016 Apr;38:116-124. doi: 10.1016/j.anaerobe.2016.01.002. Epub 2016 Jan 11.
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Virulence factors of Clostridium difficile and their role during infection.艰难梭菌的毒力因子及其在感染过程中的作用。
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Interactions Between the Gastrointestinal Microbiome and Clostridium difficile.胃肠道微生物群与艰难梭菌之间的相互作用
Annu Rev Microbiol. 2015;69:445-61. doi: 10.1146/annurev-micro-091014-104115.
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The Clostridium difficile cell wall protein CwpV confers phase-variable phage resistance.艰难梭菌细胞壁蛋白CwpV赋予噬菌体抗性的相位变异。
Mol Microbiol. 2015 Oct;98(2):329-42. doi: 10.1111/mmi.13121. Epub 2015 Aug 8.
10
The role of flagella in Clostridium difficile pathogenicity.鞭毛在艰难梭菌致病性中的作用。
Trends Microbiol. 2015 May;23(5):275-82. doi: 10.1016/j.tim.2015.01.004. Epub 2015 Feb 4.