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卡介苗转录调节因子JTY_0672的新型靶标和辅助因子库

Novel target and cofactor repertoire for the transcriptional regulator JTY_0672 from BCG.

作者信息

Wang Hui, Li Xiaotian, Wang Shuxian, Fang Ren, Xing Jiayin, Wu Ruiying, Zhang Chunhui, Li Zhaoli, Song Ningning

机构信息

Weifang Key Laboratory of Respiratory Tract Pathogens and Drug Therapy, School of Life Sciences and Technology, Shandong Second Medical University, Weifang, China.

SAFE Pharmaceutical Technology Co., Ltd., Beijing, China.

出版信息

Front Microbiol. 2025 Jan 7;15:1464444. doi: 10.3389/fmicb.2024.1464444. eCollection 2024.

DOI:10.3389/fmicb.2024.1464444
PMID:39845031
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11752888/
Abstract

(Mtb) is the pathogenic agent of tuberculosis (TB). Intracellular survival plays a central role in the pathogenesis of Mtb in a manner that is dependent on an array of transcriptional regulators for Mtb. However, the functionality of JTY_0672, a member of the TetR family of transcriptional regulators, remains unknown. In this study, EMSA, BIL, ChlP-PCR and animal models were used to investigate the regulation function of this protein. We found that the transcriptional regulator JTY_0672 is a broad-spectrum transcriptional regulatory protein and can directly regulate , both and . Cofactors containing V , V , V , V , His, Cys, Asp, Glu, Fe, Pb, Cu, and Li were found to inhibit binding between JTY_0672 and the promoter of . JTY_0672 enhanced TAG production and increased Isoniazid (INH) resistance. Besides, this protein either promoted recalcitrance to the host immune response and induced pathological injury and inflammation. In summary, this research identified new targets and cofactors of JTY_0672 and deciphered the physiological functionality of JTY_0672. Our findings will provide an important theoretical basis for understanding the Mtb transcriptional regulatory mechanism.

摘要

结核分枝杆菌（Mtb）是结核病（TB）的病原体。细胞内存活在Mtb的发病机制中起着核心作用，其方式依赖于一系列Mtb的转录调节因子。然而，转录调节因子TetR家族成员JTY_0672的功能仍然未知。在本研究中，采用电泳迁移率变动分析（EMSA）、细菌双杂交（BIL）、染色质免疫沉淀PCR（ChlP-PCR）和动物模型来研究该蛋白的调节功能。我们发现转录调节因子JTY_0672是一种广谱转录调节蛋白，可直接调节[具体调节对象未明确写出]和[具体调节对象未明确写出]。发现含有钒（V）、钒（V）、钒（V）、钒（V）、组氨酸（His）、半胱氨酸（Cys）、天冬氨酸（Asp）、谷氨酸（Glu）、铁（Fe）、铅（Pb）、铜（Cu）和锂（Li）的辅因子可抑制JTY_0672与[具体调节对象未明确写出]启动子之间的结合。JTY_0672增强了TAG的产生并增加了对异烟肼（INH）的抗性。此外，该蛋白要么促进对宿主免疫反应的抵抗并诱导病理损伤和炎症。总之，本研究确定了JTY_0672的新靶点和辅因子，并解读了JTY_0672的生理功能。我们的发现将为理解Mtb转录调节机制提供重要的理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/c977853d9ab2/fmicb-15-1464444-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/c30229382db3/fmicb-15-1464444-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/09ee2392c168/fmicb-15-1464444-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/c31346a7431f/fmicb-15-1464444-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/c02f798130d5/fmicb-15-1464444-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/2d5d2b66672e/fmicb-15-1464444-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/0623add08fbc/fmicb-15-1464444-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/73890f4044cd/fmicb-15-1464444-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/c977853d9ab2/fmicb-15-1464444-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/c30229382db3/fmicb-15-1464444-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/09ee2392c168/fmicb-15-1464444-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/c31346a7431f/fmicb-15-1464444-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/c02f798130d5/fmicb-15-1464444-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/2d5d2b66672e/fmicb-15-1464444-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/0623add08fbc/fmicb-15-1464444-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/73890f4044cd/fmicb-15-1464444-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c30/11752888/c977853d9ab2/fmicb-15-1464444-g008.jpg

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本文引用的文献

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Comprehensive structural overview of the C-terminal ligand-binding domains of the TetR family regulators.
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