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Rv0100：结核分枝杆菌中一种重要的休眠必需酰基载体蛋白。

Rv0100: An essential acyl carrier protein from M. tuberculosis important in dormancy.

机构信息

Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, United States of America.

Department of Neuropeptide Research, Central Institute for Mental Health, Mannheim, Germany.

出版信息

PLoS One. 2024 Jun 7;19(6):e0304876. doi: 10.1371/journal.pone.0304876. eCollection 2024.

DOI:10.1371/journal.pone.0304876
PMID:38848336
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11161019/
Abstract

We have identified an acyl-carrier protein, Rv0100, that is up-regulated in a dormancy model. This protein plays a critical role in the fatty acid biosynthesis pathway, which is important for energy storage and cell wall synthesis in Mycobacterium tuberculosis (MTB). Knocking out the Rv0100 gene resulted in a significant reduction of growth compared to wild-type MTB in the Wayne model of non-replicating persistence. We have also shown that Rv0100 is essential for the growth and survival of this pathogen during infection in mice and a macrophage model. Furthermore, knocking out Rv0100 disrupted the synthesis of phthiocerol dimycocerosates, the virulence-enhancing lipids produced by MTB and Mycobacterium bovis. We hypothesize that this essential gene contributes to MTB virulence in the state of latent infection. Therefore, inhibitors targeting this gene could prove to be potent antibacterial agents against this pathogen.

摘要

我们已经鉴定出一种酰基载体蛋白 Rv0100，它在休眠模型中上调。这种蛋白质在脂肪酸生物合成途径中起着关键作用，对于分枝杆菌（MTB）的能量储存和细胞壁合成很重要。与野生型 MTB 相比，敲除 Rv0100 基因会导致 Wayne 模型中非复制性持续存在中生长显著减少。我们还表明，Rv0100 对于该病原体在小鼠和巨噬细胞模型中的感染中的生长和存活是必需的。此外，敲除 Rv0100 会破坏 phthiocerol dimycocerosates 的合成，phthiocerol dimycocerosates 是 MTB 和牛分枝杆菌产生的增强毒力的脂质。我们假设该必需基因有助于潜伏感染状态下的 MTB 毒力。因此，针对该基因的抑制剂可能成为针对该病原体的有效抗菌剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08bd/11161019/facd4ed21d1e/pone.0304876.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08bd/11161019/44b3a7d18dc0/pone.0304876.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08bd/11161019/88b82ca662ba/pone.0304876.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08bd/11161019/607525b6c16e/pone.0304876.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08bd/11161019/06decfa5677a/pone.0304876.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08bd/11161019/facd4ed21d1e/pone.0304876.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08bd/11161019/44b3a7d18dc0/pone.0304876.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08bd/11161019/88b82ca662ba/pone.0304876.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08bd/11161019/607525b6c16e/pone.0304876.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08bd/11161019/06decfa5677a/pone.0304876.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08bd/11161019/facd4ed21d1e/pone.0304876.g005.jpg

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本文引用的文献

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Front Cell Infect Microbiol. 2021 Mar 16;11:635335. doi: 10.3389/fcimb.2021.635335. eCollection 2021.
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A Role for Sigma Factor C in Copper Nutritional Immunity.σ因子 C 在铜营养免疫中的作用。
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Rv0100, a proposed acyl carrier protein in Mycobacterium tuberculosis: expression, purification and crystallization. Corrigendum.
Rv0100，一种在结核分枝杆菌中被提出的酰基载体蛋白：表达、纯化及结晶。勘误
Acta Crystallogr F Struct Biol Commun. 2020 Apr 1;76(Pt 4):192-193. doi: 10.1107/S2053230X2000271X. Epub 2020 Apr 2.
4
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Acta Crystallogr F Struct Biol Commun. 2019 Oct 1;75(Pt 10):646-651. doi: 10.1107/S2053230X19012652. Epub 2019 Sep 24.
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Sci Rep. 2019 Jun 17;9(1):8667. doi: 10.1038/s41598-019-45164-5.
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