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The significance of Chromosomal Virulence Genes of Shigella flexneri in the Pathogenesis of Bacillary Dysentery

福氏志贺氏菌染色体毒力基因在细菌性痢疾发病机制中的意义

基本信息

批准号：
01440031
负责人：
YOSHIKAWA Masanosuke
金额：
$ 18.37万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1992
项目状态：
已结题

项目摘要

The essential steps leading to dysenteric symptomes by the bacterium Shigella is invasion of colonic epithelial cells, followed by intracellular bacterial multiplication and spread of invading bacteria to adjacent cells. The genetic determinants for the virulence of shigellae are located on the large 230 kb plasmid as well as on the chromosome. Extensive molecular studies have been performed on the plasmid virulence genes by the investigators from many laboratories. We also engaged in such studies in the previous project which resulted in showing that the plasmid encodes virulence-associated functions involved in intracellular invasion, secretion of virulence proteins, intra-and intercellular spreading and regulation of the expression of these plasmid-coded virulence genes. The present project was an extention of these studies aiming to clarify the significance of chromosomal virulence genes in collaboration with the plasmid genes in the pathogenesis of bacillary dysentery. The following are the summary of the results obtained:(1) Avirulent transposon insertion mutants were isolated by random transposon insertion mutagenesis. (2) The virulence-associated phenotypes of these mutants were analysed. (3) A NotI restriction cleavage map of the chromosome was constructed and the above-described mutants were assigned on it. (4) Some of the loci identified by these methods were analysed further genetically and by cellular biological techiques. These virulence-associated regions were found to be involved in either (I) LPS biosynthesis, (II) intracellular multiplication, (III) intercellular spreading, or (IV) regulation of the expression of the virulence genes on the large plasmid. For the regions classified into category (III) or (IV), a detailed analysis was made and the results have already been published as articles or reviews in international journals.

志贺氏菌引起痢疾症状的必要步骤是侵入结肠上皮细胞，随后进行细胞内细菌繁殖并将侵入细菌扩散至邻近细胞。志贺氏菌毒力的遗传决定因素位于 230 kb 大质粒以及染色体上。许多实验室的研究人员对质粒毒力基因进行了广泛的分子研究。我们在之前的项目中也进行了此类研究，结果表明质粒编码与细胞内侵袭、毒力蛋白分泌、细胞内和细胞间传播以及这些质粒编码毒力基因表达的调节相关的毒力相关功能。本项目是这些研究的延伸，旨在阐明染色体毒力基因与质粒基因合作在细菌性痢疾发病机制中的重要性。所得结果总结如下：(1)通过随机转座子插入诱变分离出无毒转座子插入突变体。 (2)分析了这些突变体的毒力相关表型。 (3)构建染色体的NotI限制性酶切图谱，并在其上分配上述突变体。 (4)对通过这些方法鉴定的一些位点进行了进一步的遗传学和细胞生物学技术分析。发现这些毒力相关区域参与 (I) LPS 生物合成、(II) 细胞内增殖、(III) 细胞间传播或 (IV) 大质粒上毒力基因表达的调节。对于分类为（III）或（IV）类的地区，进行了详细的分析，结果已在国际期刊上以文章或评论的形式发表。