在Yersinia pseudotuberculosis中的一种二酶CpdB降解了CDN,以抑制先天免疫反应
Xiao Wang1, Xinwei Hao1, Yuqing Yang1
1State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China.
Veterinary microbiology
|July 31, 2024
概括
耶尔西尼亚伪结核病使用CpdB,一个循环二核酸酸酶,降解细菌分子,通过STING途径逃避宿主免疫检测. 这一发现对于了解细菌生存和开发新疗法至关重要.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 生物化学 生化学
背景情况:
- 耶尔西尼亚伪结核病 (Yptb) 是一种病原体,可激活宿主天生的免疫力.
- 来自宿主和细菌的循环二核酸 (CDN) 可以触发免疫反应.
- 细菌水解酶降解CDN,帮助病原体在免疫逃避中.
研究的目的:
- 为了识别和描述Yptb中涉及免疫逃避的新型酸酶.
- 为了研究已识别的酶的基质特异性和活性,CpdB.
- 阐明CpdB在Yptb与宿主免疫系统的相互作用中的作用,特别是STING通路.
主要方法:
- 高性能液体染色学 (HPLC) 用于确定CpdB的降解活性.
- 构建和分析一个缺乏cpdB基因 (∆cpdB) 的Yptb突变体.
- 使用巨细胞的体外测定和使用小鼠模型的体内研究来评估免疫反应和细菌负担.
主要成果:
- CpdB特别降解细菌的CDN (c-di-AMP,c-di-GMP,3'3'-cGAMP),但不是来自宿主的2'3'-cGAMP.
- ∆cpdB突变显示细胞内c-di-GMP水平增加,并引起更强的先天免疫反应.
- CpdB以一种依赖于STING的方式抑制了Yptb诱导的先天免疫力.
- 与野生型Yptb.相比,感染了∆cpdB的小鼠的细菌负担较低.
结论:
- CpdB是一种Yptb循环二核酸酸酶,对于逃避宿主免疫监测至关重要.
- 细菌CDN受到CpdB的降解会抑制由STING介导的先天免疫反应.
- CpdB在宿主体内的Yptb的生存和病变发生中发挥着重要作用.
相关概念视频
GPCRs Regulate Adenylyl Cylase Activity
5.4K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.4K
Inhibition of Cdk Activity
4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K
IP3/DAG Signaling Pathway
12.0K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.0K
Negative Regulator Molecules
35.3K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.3K
GPCR Desensitization
5.9K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
5.9K
Phosphoinositides and PIPs
8.5K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.5K


