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

本研究的结果表明，1.化脓性链球菌内化进入人咽上皮细胞的频率较高。此外，化脓性链球菌透明质酸的存在降低了入侵效率。所有化脓性链球菌均含有fbp54基因，编码纤维连接蛋白结合蛋白FBP54，有望成为预防化脓性链球菌感染的疫苗。化脓性链球菌在上皮细胞的内化是诱导细胞凋亡的必要条件和充分条件，线粒体功能障碍是诱导细胞凋亡的必要和充分条件，而化脓性链球菌诱导细胞凋亡的机制与志贺氏菌、沙门氏菌等其他细胞内侵袭性细菌明显不同。蛋白FBA促进化脓性链球菌进入人上皮细胞。该蛋白具有三个或四个富含脯氨酸的重复结构域，与金黄色葡萄球菌的纤维连接蛋白结合蛋白FnBPA具有很高的同源性。FBA基因在化脓性链球菌的M型1、2、4、22、28和49型中被发现，并受MGA调节子的调控。给予超抗原可以保护小鼠免受李斯特菌等细胞内细菌的感染，这依赖于在有CD4^+T细胞存在的情况下李斯特菌特异性CTL活性的增强，并且超抗原在针对细胞内病原体的免疫中显示出佐剂活性。LBP蛋白具有层粘连蛋白结合活性，并参与与咽上皮细胞的黏附。

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.