Molecular mechanisms of bacterial toxins on host cells

细菌毒素对宿主细胞的分子机制

• 批准号: 04304032
• 负责人: NAKANO Masayasu
• 金额: $ 9.6万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Co-operative Research (A)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04304032/
• 关键词: Bacterial toxins; Endotoxin; Lipopolysaccharide; Exotoxin; Cytotoxic toxins; 細胞傷害; LPS; 蛋白毒素; GPIアンカー

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.

1. 细胞内毒素（内毒素和微囊毒素）的研究：(A) LPS（内毒素）：LPS诱导小鼠腹腔巨噬细胞产生tnf - α依赖于蛋白激酶Cbeta，而il -1 β的产生主要依赖于钙调素。肾上腺皮质激素参与lps诱导的小鼠胸腺细胞凋亡。P.gingivalis LPS激活对LPS无反应的C3H/HeJ B细胞中的酪氨酸激酶。(B)微囊藻毒素对大鼠肝细胞的损伤部分依赖于非实质肝细胞产生的细胞毒性介质。外毒素的研究：No.167（谷氨酸）和170号A亚基n端（精氨酸）氨基酸对Vero毒素的细胞毒活性至关重要。靶细胞膜上的蛋白酶是白喉毒素活化的必要条件。副溶血弧菌的溶血毒素TDH在与受体结合后使红细胞中的25kDa蛋白磷酸化。从靶细胞中纯化出霍乱毒素增强子（ARFs）和抑制子（ARIs）。阐明了ST1毒素穿透螺旋菌内膜的机理。将ST毒素受体基因转染COS7细胞，并对产物进行分析。艰难梭菌产生一种与毒素a不同的红细胞凝集素，破伤风毒素释放神经递质依赖于钙调素。产李斯特溶素o的单增李斯特菌仅能在感染宿主体内诱导炎性细胞因子mrna，并赋予其细胞免疫功能。a群链球菌产生的蛋白酶SH可能参与感染性休克的发生。超级抗原可引起猩红热、耶尔森氏菌和川崎病的症状。

项目成果

Honda,T 他: "The pathogenicity of Vibrio parahaemolyticus and the role of the thermostable direct haemolysin and related haemolysins" Reviews in Medical Microbiology. 4. 106-113 (1993)

Honda, T 等人：“副溶血弧菌的致病性以及热稳定性直接溶血素和相关溶血素的作用”医学微生物学评论 4. 106-113 (1993)。

Takeda, Y.et al.: "Vero toxins (Shiga-like toxins) produced by enterohemorrhagic Esherichia coli (Vero-cytotoxin-producing E.coli)." Microbiol.Immunol.37. 591-599 (1993)

Takeda, Y.等人：“由肠出血性大肠杆菌（产Vero细胞毒素的大肠杆菌）产生的Vero毒素（志贺样毒素）。”

Tsuneoka, M.et al.: "Evidence for involvement of furin in cleavage and activation of diphtheria toxin." J.Biol.Chem.268. 26464-26465 (1993)

Tsuneoka, M.等人：“弗林蛋白酶参与白喉毒素裂解和激活的证据。”

Zhag,Y.-H.他: "Invivs in duction of apoptosis (programmed cell death)in mouse Inymuo by administration of LPS" Infection and Immunity. 61. 5044-5047 (1993)

Zhag, Y.-H. 等人：“通过施用 LPS 诱导小鼠 Inymuo 细胞凋亡（程序性细胞死亡）”《感染与免疫》61. 5044-5047 (1993)

Yokochi, T. et al.: "Novel adjuvant action of lipopolysaccharides that possess mannose homopolysaccharides as O-specific polysaccharides on immune response to nonimmunogenic antoantigens in mice" Infect. Immun.60. 4953-4956 (1992)

Yokochi, T. 等人：“具有甘露糖同多糖作为 O 特异性多糖的脂多糖对小鼠非免疫原性抗原的免疫反应具有新的佐剂作用”感染。