Molecular mechanisms of bacterial toxins on host cells

1.细胞内毒素(内毒素和微囊藻毒素)的研究：(A)内毒素：内毒素诱导的小鼠巨噬细胞产生肿瘤坏死因子-α依赖于蛋白激酶Cβ，而产生IL-1β主要依赖于钙调素。肾上腺皮质激素参与了内毒素诱导的小鼠胸腺细胞的凋亡。牙龈假单胞菌脂多糖激活脂多糖无反应的C3H/HeJ B细胞中的酪氨酸激酶。(2)微囊藻毒素对大鼠肝细胞的损伤作用部分依赖于非实质肝细胞产生的细胞毒介质。外毒素的研究：A亚基N端的167号(谷氨酸)和170号(精氨酸)氨基酸是Vero毒素细胞毒活性所必需的。白喉毒素的激活离不开靶细胞膜上的蛋白水解酶呋喃。副溶血性弧菌的溶血毒素TdH与受体结合后，使红细胞中的25 kDa蛋白磷酸化。从靶细胞中纯化霍乱毒素的增强子(ARF)和抑制子(ARIS)。阐明了ST1毒素穿透螺旋杆菌内膜的机理。将ST毒素受体基因导入COS7细胞，并对表达产物进行分析。艰难梭菌产生一种不同于A毒素的红细胞凝集素。破伤风毒素依赖钙调蛋白释放神经递质。单核细胞增多性李斯特菌溶血素O产生菌只能在感染宿主体内诱导炎性细胞因子mRNAs，并赋予其细胞免疫功能。A群链球菌产生的蛋白水解酶SH可能参与了感染性休克。超抗原可能会引起Scalet热、耶尔森氏菌和川崎病的症状。

1. Research for intracellular toxins (endotoxins and microcystins) :(A) LPS (endotoxins) : LPS-induced TNF-alpha production by the murine peritoneal macrophages is dependent on protein kinase Cbeta, but the production of IL-1beta depends mainly on calmodulin.adrenocorticoides participate in LPS-induced murine thymocyte apoptosis. P.gingivalis LPS activates tyrosine kinases in LPS-nonresponsive C3H/HeJ B cells. (B) Damage of rat liver cells by microcystin is partialy dependent on the cytotoxic mediators produced by non-parenchymal liver cells.2. Research for exotoxins :No.167 (glutamic acid) and no.170 (arginine) amino acids from N-terminal of A subunit are essential for the cytotoxic activity of Vero toxin. Protease, furin, in target cell membrane is essential for activation of diphthelia toxin. Hemolytic toxin, TDH, of V.parahemolytics phosphorylates 25kDa protein in red blood cells after binding the receptors. The enhancer (ARFs) and suppressor (ARIs) of cholera toxin were purified from target cells. The mechnisms on penetration of ST1 toxin through inner membrane of E.coil was clarified. The receptor gene for ST toxin was transfected to COS7 cells and the products were analyzed. C.difficile produces a red blood cell agglutinin which is different from toxin A.The release of neurotransmitter by tetanus toxin depends on calmodulin. The listerolysin O-producing strains of L.monocytogenes only can induce inflamatory cytokine mRNAs in infected hosts and endow them the cellular immunity. Protease SH produced by A-group streptococci may be participated in septic shock. Super-antigens may cause scalet fever, symptomes of Yersinia and Kawasaki disease.