在Acinetobacter Baumannii分泌的蛋白酶CpaA抑制了因子XII介导的布拉迪基宁生成和中性粒细胞激活
Kris M Blair1,2, Dillon J Bohinc3, Kara L Bane3
1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor. (K.M.B., B.A., C.G., M.X.O., M.S.).
Circulation research
|May 13, 2025
概括
这种细菌是Acinetobacter baumannii.
科学领域:
- 血栓炎症和天生的免疫研究.
- 凝血因子XII (FXII) 和卡利克林-基宁系统 (KKS) 的相互作用.
- 细菌金属蛋白酶和宿主-病原体相互作用.
背景情况:
- 凝血因子XII (FXII) 对于接触激活,凝血和炎症至关重要.
- FXIIa激活了prekallikrein,导致布拉迪基宁生成并促进炎症.
- Acinetobacter baumannii分泌CpaA,这是一个裂开FXII的金属蛋白酶,但其在人类感染中的作用尚不清楚.
研究的目的:
- 阐明CpaA,FXII和kallikrein-kinin系统 (KKS) 之间的结构相互作用.
- 为了确定CpaA对血栓炎症反应的影响.
- 调查CpaA在细菌病原和免疫逃避中的作用.
主要方法:
- 描述CpaA对FXII凝固剂活性和布拉迪基宁生成的影响.
- 评估中性粒细胞信号传递,流细胞计和功能测试,以评估CpaA对先天免疫的影响.
- 用野生型和CpaA缺乏的A. baumannii菌株对人类中性粒细胞杀死细菌的评估.
主要成果:
- 通过CpaA切割FXII细胞因子和FXIIa,阻止FXII的激活,但没有显著抑制FXIIa的凝固活动.
- 在CpaA中,高分子量基因因素 (HK) 被分裂,减少了卡利克林激活和布拉迪基宁生成.
- 中性粒细胞FXII的CpaA介导裂变会损害中性粒细胞的激活,包括减少Akt2酸化,化学反应,氧化突发和NET形成,降低杀死细菌的效率.
结论:
- FXII在宿主对细菌感染的反应中发挥着重要作用.
- CpaA 抑制了接触激活和 KKS,从而抑制了先天免疫反应.
- 通过损害中性粒细胞激活和细菌清除,CpaA可能促进Acinetobacter baumannii的生存.
相关概念视频
01:24Caspases
8.7K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
8.7K
01:31The Intrinsic Apoptotic Pathway
6.2K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K
01:09GPCRs Regulate Adenylyl Cylase Activity
6.9K
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...
6.9K
01:20Extrinsic and Intrinsic Pathways of Hemostasis
11.1K
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
11.1K
01:28Gene Regulation in Microbial Communities: Quorum Sensing
966
Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
966
01:21Acute Pancreatitis II: Pathophysiology
52
The pathophysiology of acute pancreatitis centers on injury to pancreatic acinar cells, which initiates a cascade of harmful intracellular events.This injury leads to premature activation of trypsinogen to trypsin in the pancreas. Trypsin then activates other digestive enzymes, such as chymotrypsin, elastase, and phospholipase A2, which begin breaking down pancreatic tissue. The resulting autodigestion causes local inflammation, tissue swelling, hemorrhage, and fat necrosis.Injured acinar cells...
52