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必需基因胸苷酸合成酶参与宿主内的免疫调节和存活。

Essential Gene Thymidylate Synthase Is Involved in Immune Modulation and Survival inside the Host.

作者信息

Tanweer Sana, Sharma Tarina, Grover Abhinav, Agarwal Meetu, Grover Sonam

机构信息

Department of Molecular Medicine, Jamia Hamdard, New Delhi-110065, India.

New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, United States.

出版信息

ACS Omega. 2024 Jul 23;9(31):33743-33750. doi: 10.1021/acsomega.4c02919. eCollection 2024 Aug 6.

DOI:10.1021/acsomega.4c02919
PMID:39130601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11308015/
Abstract

A essential gene, ThyX (Rv2754c), plays a key role in intermediate metabolism and respiration by catalyzing the formation of dTMP and tetrahydrofolate from dUMP and methylenetetrahydrofolate. ThyX is present in the complex and in a nonpathogenic strain of Mycobacteria. In this study, we identified a novel function of ThyX, an enzyme with immune-modulating properties. We have shown that ThyX can activate the macrophages in the host toward M1 response. Overexpression of ThyX stimulates the production of nitrite oxide (NO) and induces apoptosis in macrophages; indeed both responses help the host to control growth of . ThyX was also discovered to play a role in the recombinant bacterium's ability to survive when it was subjected to oxidative and hypoxic stress by macrophages. These findings demonstrate the protein's functional importance in . Indeed these findings represent ThyX as a potential candidate for future research and show this as a therapeutic target.

摘要

一个必需基因,ThyX(Rv2754c),通过催化由dUMP和亚甲基四氢叶酸形成dTMP和四氢叶酸,在中间代谢和呼吸中起关键作用。ThyX存在于结核分枝杆菌的复合体和非致病菌株中。在本研究中,我们鉴定了ThyX的一种新功能,它是一种具有免疫调节特性的酶。我们已经表明,ThyX可以激活宿主中的巨噬细胞向M1反应。ThyX的过表达刺激一氧化氮(NO)的产生并诱导巨噬细胞凋亡;事实上,这两种反应都有助于宿主控制结核分枝杆菌的生长。还发现ThyX在重组细菌受到巨噬细胞的氧化和缺氧应激时的存活能力中起作用。这些发现证明了该蛋白在结核分枝杆菌中的功能重要性。确实,这些发现表明ThyX是未来研究的潜在候选者,并显示其为治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94e/11308015/acd5d88d2fba/ao4c02919_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94e/11308015/5108f03c16bf/ao4c02919_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94e/11308015/1ae16166d42d/ao4c02919_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94e/11308015/32569b4919c4/ao4c02919_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94e/11308015/243bef4394b2/ao4c02919_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94e/11308015/acd5d88d2fba/ao4c02919_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94e/11308015/5108f03c16bf/ao4c02919_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94e/11308015/1ae16166d42d/ao4c02919_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94e/11308015/32569b4919c4/ao4c02919_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94e/11308015/243bef4394b2/ao4c02919_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94e/11308015/acd5d88d2fba/ao4c02919_0005.jpg

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本文引用的文献

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WHO's Global Tuberculosis Report 2022.世界卫生组织《2022年全球结核病报告》。
Lancet Microbe. 2023 Jan;4(1):e20. doi: 10.1016/S2666-5247(22)00359-7. Epub 2022 Dec 12.
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Methyltransferase Rv1515c Can Suppress Host Defense Mechanisms by Modulating Immune Functions Utilizing a Multipronged Mechanism.甲基转移酶Rv1515c可通过多种机制调节免疫功能来抑制宿主防御机制。
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2020 年全球结核病报告——对全球结核病负担、治疗和预防工作的反思。
Int J Infect Dis. 2021 Dec;113 Suppl 1(Suppl 1):S7-S12. doi: 10.1016/j.ijid.2021.02.107. Epub 2021 Mar 11.
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Mycobacterium tuberculosis thymidylate synthase (ThyX) is a target for plumbagin, a natural product with antimycobacterial activity.结核分枝杆菌胸苷酸合酶(ThyX)是一种天然产物染料木黄酮的作用靶点,染料木黄酮具有抗分枝杆菌活性。
PLoS One. 2020 Feb 4;15(2):e0228657. doi: 10.1371/journal.pone.0228657. eCollection 2020.
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Targeting Methyltransferases in Human Pathogenic Bacteria: Insights into Thymidylate Synthase (TS) and Flavin-Dependent TS (FDTS).靶向人类致病菌中的甲基转移酶:胸苷酸合成酶(TS)和黄素依赖性 TS(FDTS)的研究进展。
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Role of Oxidative Stress in the Pathology and Management of Human Tuberculosis.氧化应激在人类结核病的病理和治疗中的作用。
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Methylation in Mycobacterium tuberculosis is lineage specific with associated mutations present globally.分枝杆菌中的甲基化是谱系特异性的,全球范围内存在相关突变。
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M. tuberculosis-Induced Necrosis of Infected Neutrophils Promotes Bacterial Growth Following Phagocytosis by Macrophages.结核分枝杆菌感染的中性粒细胞坏死促进吞噬后的巨噬细胞内细菌生长。
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