Studies on biological modifier produced by bacteria

1)本课题的研究内容之一是探讨细菌肠毒素在肠组织中的信号转导机制。在大肠杆菌耐热肠毒素（ST）引起的水样腹泻中，发现环鸟苷酸依赖性蛋白激酶（cGMP-dependent protein kinase）的激活是其信号转导的必要步骤，其中一种蛋白质是环鸟苷酸依赖性蛋白激酶（cGMP-dependent protein kinase），（81K-，43 K-和37 K- dalfons）也被环AMP-磷酸化。依赖性蛋白激酶在肠细胞暴露于霍乱肠毒素。这一发现表明，ST和胆肠毒素通过共同的机制后，增加环核苷酸含量在肠组织中的主要作用。在假单胞菌杀白细胞素的作用中观察到类似的信号转导途径，即在溶酶体蛋白磷酸化后，激活多形核白细胞的依赖于Ca^（2+）的蛋白激酶。2）对许多肠致病性病原菌产生的热稳定肠毒素的结构进行了详细的比较，发现它们具有与热稳定性和生物活性相关的共同结构。对霍乱肠毒素结构的免疫学研究为研制新型有效的霍乱疫苗提供了理论依据。3）细菌内毒素能刺激T细胞释放白细胞介素，促进T细胞生长，表明细菌内毒素在免疫应答中具有重要作用。

1) The mechanism of signal trunsduction of bacterial enterotoxin in intestinal tissue was investigated as one of the projects. In watery diarrhea caused by heat-stable enterotoxin (ST) of Enterotoxigenic Escherichia coli, it was found that an activation of cyclic GMP dependent protein kinase is a necessary step in its signal transduction and that one of the proteins (81K-, 43K- and 37K- dalfons) phosphorylated by cyclic GMP-dependent protein kinase was also phosphorylated by cyclic AMP-dependent protein kinase in itestinal cells exposed to cholera enterotoxin. This finding suggests that ST and cholear enterotoxin work through a common mechanism after increase of cyclic nucleotide content in intestinal tissue by their primary actions. Similar signal trunsduction pathway was observed in the action of Pseudomonal leukocidin by which <Ca^(2+)> -dependent protein knase of polymorphonuclear leukocyte was activated, following phosphorylation of lysosomal protein.2) A detailed comparison of structural analysis of heat-stable enterotoxins produced by many enterotoxigenic pathogens indicated the common structure related to heat stability and biological activity. Immunological studies on the structure of cholera enterotoxin suggests the development of new effective vaccine against cholera.3) It was found that bacterial lipopolysaccharide stimulated the release of interleukin from T cell and enhanced the growth of the cell, indicating the significant role of LPS in immune response.