关键的组织点负责炭毒素诱导的致死性.
Shihui Liu1, Yi Zhang, Mahtab Moayeri
1Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. shliu@niaid.nih.gov
Nature
|September 3, 2013
概括
炭杆菌毒素通过破坏不同的细胞类型导致致死性. 炭病致死毒素 (LT) 针对心脏和血管细胞,而胀毒素 (ET) 主要影响肝细胞 (肝细胞).
科学领域:
- 微生物学 微生物学
- 毒理学 毒理学 毒理学
- 病理生理学 病理生理学
背景情况:
- 炭杆菌通过两个外毒素引起炭:致命毒素 (LT) 和瘤毒素 (ET).
- 负责这些毒素致命作用的特定宿主细胞点仍然未被确定.
- 毛细血管形态发生蛋白-2 (CMG2) 是这些毒素的已知受体.
研究的目的:
- 阐明炭病致命毒素 (LT) 和水毒素 (ET) 准的关键细胞类型,导致宿主死亡.
- 研究炭毒素受体CMG2在不同细胞类型中中介毒素诱导致死性的作用.
主要方法:
- 生产特定细胞类型的CMG2-无和CMG2-表达的小鼠.
- 挑战这些转基因小鼠用纯化的炭致命毒素 (LT) 和瘤毒素 (ET).
- 评估特定细胞类型对毒素诱导死亡率的贡献.
主要成果:
- 来自LT的致死性涉及心肌细胞和血管光滑肌细胞的损伤.
- ET诱导的致死性主要通过其对肝细胞的作用进行介导.
- 与之前的假设相反,LT或ET对内皮细胞的向不会对死亡率有显著的贡献.
结论:
- 炭杆菌使用LT和ET诱导宿主致命性,通过协调损害不同的重要器官系统.
- LT和ET表现出差异性的细胞类型热带性,针对单独的关键细胞群产生致命效应.
- 内皮细胞不是炭杆毒素诱导的致死性的主要目标.
相关概念视频
Bacterial Toxins
Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
Diphtheria
Diphtheria is an acute, toxin-mediated infectious disease that primarily affects the upper respiratory tract. It is caused by Corynebacterium diphtheriae, a Gram-positive, pleomorphic rod that lacks spore-forming capability and exhibits a characteristic club-shaped morphology under microscopic examination. While C. diphtheriae can asymptomatically colonize mucosal surfaces, clinical disease manifests only when the bacterial strain is lysogenized by a specific β-corynephage. This phage...
Receptor-mediated Endocytosis
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Cytotoxic T Cells-mediated Immune Response
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Bacterial Gastroenteritis
Bacterial gastroenteritis, characterized by diarrhea, abdominal cramps, and vomiting, is often caused by ingestion of contaminated food or water and is frequently associated with pathogenic Escherichia coli strains. These microbes exploit two principal mechanisms to inflict disease.Shiga toxin–producing E. coli, also referred to as STEC—notably O157:H7—release Shiga toxins that target ribosomes, blocking protein synthesis. The B subunit of the toxin binds the host glycolipid receptor...
Toxicity Testing in Animals
Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...


