来自人类病原体沙门氏菌 Typhi 的细菌毒素的宿主适应
Lingquan Deng1, Jeongmin Song2, Xiang Gao2
1Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Cell
|December 7, 2014
概括
沙门氏菌类毒素通过与Neu5Ac糖结合来向人体细胞. 表达Neu5Gc的小鼠具有耐药性,这揭示了沙门氏菌Typhi的分子基础.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 沙门氏菌 Typhi 导致伤寒发烧,这是一种重要的人类疾病.
- 伤寒毒素是导致疾病症状的关键毒性因素.
- 毒素的活性是通过结合细胞表面上的化甘来调节的.
研究的目的:
- 为了研究伤寒毒素与不同化甘氨酸的结合特异性.
- 阐明沙门氏菌Typhi宿主特异性背后的分子机制.
- 为了确定伤寒热的潜在治疗点.
主要方法:
- 对结热毒素与表达人类 (Neu5Ac) 和哺乳动物 (Neu5Gc) 甘的细胞结合的分析.
- 在小鼠模型中评估毒素毒性,包括表达CMAH的小鼠模型.
- 确定结合Neu5Ac.Ac.的伤寒毒素的原子结构.
主要成果:
- 伤寒毒素优先结合并对表达N-乙神经胺酸 (Neu5Ac) 终结型甘氨酸的细胞有毒.
- 构成性表达N-glycolylneuraminic酸 (Neu5Gc) 的小鼠对伤寒毒素有抗性.
- 原子结构揭示了毒素和Neu5Ac.之间的特定结合相互作用.
结论:
- 与Neu5Ac与Neu5Gc的结合差异解释了沙门氏菌Typhi的独特人类宿主特异性.
- 了解这些分子相互作用为病原体与宿主相互作用提供了见解.
- 这些发现可能有助于开发新的伤寒热病疗法.
相关概念视频
Bacterial Toxins
109
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...
109
Receptor-mediated Endocytosis
12.8K
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...
12.8K
Bacterial Gastroenteritis
70
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...
70
Other Stress Responses in Bacteria
560
Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
560
Regulation of Bacterial Virulence
66
Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...
66
Defense Against Bacterial Pathogens
3.7K
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
3.7K


