布鲁塞拉Omp25激活了未折叠的蛋白质反应,促进细胞内增殖和炎症
Jin-Ke Yang1, Shuang Huang1, Yuan-Pan Hou1
1State Key Laboratory of Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou, China.
The Journal of biological chemistry
|February 28, 2026
概括
布鲁塞拉细菌使用外膜蛋白Omp25来激活宿主.
科学领域:
- 微生物学和免疫学
- 细胞生物学 细胞生物学
- 传染性疾病 传染性疾病
背景情况:
- 血病是一种由Brucella细菌引起的动物性疾病,这种细菌在细胞内复制,主要是在内质网膜 (ER) 中.
- 细菌对宿主ER及其应激反应途径的操纵,如未展开的蛋白质反应 (UPR),对于病变发生至关重要,但了解不够.
- 在ER陪伴者BiP和UPR传感器 (PERK,IRE1α,ATF6) 是ER恒温的关键调节器.
研究的目的:
- 研究布鲁塞拉外膜蛋白Omp25在调节宿主UPR通路中的作用.
- 阐明Omp25促进细菌细胞内生存和发病的机制.
- 评估Omp25作为一种潜在的治疗病的标.
主要方法:
- 确定Omp25作为参与布鲁塞拉诱导的UPR激活的因素.
- 实验室内研究涉及带有和没有Omp25 (Δomp25) 和宿主细胞培养的细菌菌株.
- 对蛋白质-蛋白质相互作用 (Omp25-BiP),UPR传感器激活,炎症性细胞因子表达和细菌复制的分析.
- 在体内研究使用小鼠brucellosis模型来评估细菌负担和组织病理.
主要成果:
- 布鲁塞拉外膜蛋白Omp25直接与ER护卫BiP结合,激活UPR传感器PERK,IRE1α和ATF6.6,从而使UPR传感器变得更活跃.
- Omp25调节ER稳态,有利于细菌复制,并通过BiP-IRE1α-NF-κB通路增强炎症性细胞因子的产生.
- Δomp25突变菌株表现出细胞内复制受损,UPR激活减少,以及减弱的炎症基因诱导.
- 与野生型感染相比,感染 Δomp25 突变体的小鼠表现出较低的细菌负载和较少的组织损伤.
结论:
- 布鲁塞拉Omp25是一种关键的毒性因子,通过劫持宿主UPR来促进细菌的增殖.
- Omp25对UPR传感器和炎症途径的激活有助于布鲁塞拉病变.
- Omp25是开发新型抗牛肉治疗方法和减弱疫苗的有希望的目标.
关键词:
这就是BiP BiP BiP.布鲁塞拉病毒是什么?Omp25 Omp25 Omp25 Omp25 Omp25 Omp25 Omp25 Omp25 Omp25 Omp25 Omp25 Omp25这是一种炎症炎症炎症炎症.展开的蛋白质反应 (UPR)更多相关视频
10:12Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
Published on: June 14, 2024
2.7K
08:34Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
12.0K
相关概念视频
01:31Regulation of the Unfolded Protein Response
3.1K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.1K
01:37The Unfolded Protein Response
6.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.6K
01:23Stringent Response in E. coli
420
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
420
02:23Abnormal Proliferation
5.3K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K
01:16TGF - β Signaling Pathway
10.7K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.7K
01:22PI3K/mTOR/AKT Signaling Pathway
5.9K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.9K