Molecular analyses on Streptococcus pyogenes adherence to and invasion of pharyngeal epithelial cells

化脓性链球菌对咽上皮细胞粘附和侵袭的分子分析

• 批准号: 11307039
• 负责人: HAMADA Shigeyuki
• 金额: $ 9.56万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11307039/
• 关键词: Streptococcus pyogenes; Invasion; Fibronectin; Vaccine; Extracellular matrix; Laminin; Adhesion; フィプロネクチン; 細胞マトリックス; 体液性免疫; 莢膜; ヒアルロン酸; 上皮細胞; hasA

The results obtained by this study suggest that1. Streptococcus pyogenes can be internalized into human pharyngeal epithelial cells with considerably high frequencies. Furthermore, the presence of hyaluronic acid of S. pyogenes decreases the invasion efficiency.2. All the S. pyogenes strains possess the fbp54 gene encoding fibronectin-binding protein FBP54, which is a promising vaccine for the prevention of S. pyogenes infections.3. The internalization of S. pyogenes in epithelial cells is necessary and sufficient for the induction of apoptosis, which is initiated by mitochondrial dysfunction, and the mechanism of S. pyogenes-induced apoptosis is clearly different from that induced by other intracellular invasive bacteria, e.g. Shigella and Salmonella species.4. Protein Fba promotes S. pyogenes entry into human epithelial cells. This protein possesses three or four proline-rich repeat domains and exhibits a high homology to FnBPA, the fibronectin-binding protein of Staphylocaccus aureus. The fba gene is found in M types 1, 2, 4, 22, 28, and 49 of S. pyogenes, and is transcribed under the control of the Mga regulator.5. Administration of superantigens protect mice from infection with intracellular bacteria such as Listeria, which is dependent on the enhanced Listeria-specific CTL activity in the presence of CD4^+ T cells, and superantigens exhibit adjuvant activity in the immunization against intracellular pathogens.6. Protein Lbp possesses laminin-binding activity and is involved in adhesion to pharyngeal epithelial cell.

研究结果表明：1.化脓性链球菌能够以相当高的频率内化到人咽上皮细胞中。此外，S.化脓性链球菌降低了侵袭效率.所有的S。化脓性链球菌菌株具有编码纤维连接蛋白结合蛋白FBP54的fbp54基因，其是预防化脓性链球菌的有希望的疫苗。化脓性感染。S.的内化。化脓性链球菌感染上皮细胞是诱导细胞凋亡的必要条件和充分条件，细胞凋亡是由线粒体功能障碍引起的，化脓性链球菌感染的机制尚不清楚。化脓性链球菌诱导的细胞凋亡明显不同于其他细胞内侵入性细菌（例如志贺氏菌和沙门氏菌属）诱导的细胞凋亡。Fba蛋白促进S.化脓菌进入人体上皮细胞。该蛋白具有三个或四个富含脯氨酸的重复结构域，并与金黄色葡萄球菌的纤连蛋白结合蛋白FnBPA具有高度同源性。fba基因存在于1、2、4、22、28和49型沙门氏菌中。化脓性链球菌，并且在Mga调节子的控制下转录。施用超抗原可保护小鼠免受李斯特菌等细胞内细菌的感染，这依赖于在CD4^+ T细胞存在下增强的李斯特菌特异性CTL活性，并且超抗原在针对细胞内病原体的免疫中表现出佐剂活性。Lbp蛋白具有层粘连蛋白结合活性，并参与咽上皮细胞的粘附。

项目成果

Terao Y., et al.: "Fba, a novel fibronectin-binding protein from Streptococcus pyogenes, promotes bacterial entry into epithelial cell, and the fba gene is positively transcribed under the Mga regulator"Molecular Microbiology. 42・1. 75-86 (2001)

Terao Y. 等人：“Fba 是一种来自化脓性链球菌的新型纤连蛋白结合蛋白，可促进细菌进入上皮细胞，并且 fba 基因在 Mga 调节因子的作用下进行正转录”《分子微生物学》42・1。 (2001)

Okamoto et al.: "Administration of superantigens protects mice from lethal Listeria monocytogenes inection pyenhancing cytotoxic T cells"Infect. Immun.. 69. 6633-6642 (2001)

Okamoto 等人：“施用超级抗原可保护小鼠免受致命的单核细胞增生李斯特菌感染，增强细胞毒性 T 细胞”感染。

Terao Y et al.: "Fba, a novel fibronectin-binding protein from Streptococcus pyogenes, promotes bacterial entry into epithelial cells, and the fba gene is positively transcribed under the Mga regulator."Mol Microbiol. 42. 75-86 (2001)

Terao Y 等人：“Fba 是一种来自化脓性链球菌的新型纤连蛋白结合蛋白，可促进细菌进入上皮细胞，并且 fba 基因在 Mga 调节因子下正向转录。”Mol Microbiol。

Fujiwara,T. et al.: "Glucosyltransferase from Streptococcus oralis : purification, characterization, and molecular analysis of its gene"Infection and Immunity. 68・5. 2475-2486 (2000)

Fujiwara, T. 等人：“口腔链球菌的葡萄糖基转移酶：其基因的纯化、表征和分子分析”感染和免疫 68·5 (2000)。

Kawabata,S.et al.: "Molecular cloning,sequence, and characterization of a novel streptococcal phosphoglycerate dehydrogenase gene"Oral Microbiology and Immunology. 15・1. 58-62 (2000)

Kawabata, S. 等人：“新型链球菌磷酸甘油酸脱氢酶基因的分子克隆、序列和表征”口腔微生物学和免疫学 15·1 (2000)。