Comprehensive analyses of bacterial pathogenesis based on the genome information

基于基因组信息的细菌致病机制综合分析

基本信息

批准号：
14014241
负责人：
HAYASHI Tetsuya
金额：
$ 45.12万
依托单位：
University of Miyazaki (2004)宮崎医科大学 (2002-2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14014241/
关键词：
pathogenic Escherichia coli Clostridium perfringens Vibrio parahaemolyticus pathogenicity Genomic diversity gene regulatory network two component regulatory system Type III secretion system 腸炎ビブリオゲノムマイクロアレイ 2成分制御系 PCR

项目摘要

In this research, we performed a comprehensive analysis of the pathogenesis and genomic diversity of three important pathogenic bacteria based on their genome sequences, and obtained followings major findings.1. Pathogenic Escherichia coli:(1) Based on the O157 Sakai sequence, we developed ○a microarray and the whole genome PCR scanning method. (2) By using these two methods, we performed a large-scale genomic comparison of O157 and non-O157 enterohemorrhagic E. coli (EHEC) strains, and revealed that there exits a remarkable genomic diversity among O157 strains, and that variation of prophages and IS elements are major factors to generate this genomic diversity. Furthermore, we revealed that non-O157 EHEC strains contain a large amount of DNAs that are not present in O157. (3) We found that the RcsCDB two component regulatory system and the bicarbonate-sensing system control the virulence gene expression, and discovered novel regulators, GrvA and Pch, that are involved in these regulat … More ion systems by expression profiling anakyses using the microarray. This provided the first clue to understand how the virulence gene expression systems of pathogenic E. coli are incorporated into the intrinsic regulatory network of E. coli. (4) By employing a proteomic approach, we discovered many new effectors for the type III secretion system (TTSS) of O157.2. Clostridium perfringen :(1) The genome sequence of strain 13 was determined. (2) By using the microarray constructed based on its genome sequence, we identified 141 genes that are controlled by the VirR/S two component regulatory system or the VirR/S-VR-RNA system. They included not only virulence genes but also many genes for energy production and metabolism, indicating that genes for virulence and growth in host tissues are coordinately regulated by the VirR/S-VR-RNA system. (3) By searching the VirR-binding sequences, we identified two novel regulatory RNAs.3. Vibrio parahaemolyticus :(1) The genome sequence of strain RIMD2210633 was determined. (2) We identified two TTSSs (TTSS1 and TTSS2) on its genome, and found that TTSS1 is involved in cell toxicity and TTSS2 in diarrheagenicity. (3) We identified several effectors for each TTSS, and found that the two TTSS s exhibit distinct effector-specificities. Less

本研究根据三种重要病原菌的基因组序列，对其发病机制和基因组多样性进行了全面分析，得到以下主要发现：（1）基于O157 Sakai序列，我们开发了致病性大肠杆菌。 ○微阵列和全基因组PCR扫描方法（2）利用这两种方法，我们对O157和非O157肠出血性大肠杆菌进行了大规模的基因组比较。 (EHEC)菌株，并揭示O157菌株之间存在显着的基因组多样性，并且原噬菌体和IS元件的变异是产生这种基因组多样性的主要因素。此外，我们还发现非O157 EHEC菌株含有大量的基因组多样性。 (3)我们发现RcsCDB二元调控系统和碳酸氢盐传感系统控制毒力基因表达，并发现了新的调控因子， GrvA 和 Pch 通过使用微阵列进行表达谱分析来参与这些调节离子系统，这为了解致病性大肠杆菌的毒力基因表达系统如何纳入大肠杆菌的内在调节网络提供了第一个线索。 (4)通过采用蛋白质组学方法，我们发现了产气荚膜梭菌O157.2的III型分泌系统(TTSS)的许多新效应子。 :(1)确定了菌株13的基因组序列。(2)利用根据其基因组序列构建的微阵列,我们鉴定了141个受VirR/S二元调控系统或VirR/S-VR控制的基因。 -RNA系统。它们不仅包括毒力基因，还包括许多能量产生和代谢的基因，表明宿主组织中的毒力和生长基因受到VirR/S-VR-RNA系统的协调调节(3)。 VirR结合序列，我们鉴定了两个新的副溶血性弧菌：（1）确定了菌株RIMD2210633的基因组序列（2）我们在其基因组上鉴定了两个TTSS（TTSS1和TTSS2），发现TTSS1是。涉及细胞毒性，TTSS2 涉及致泻性 (3) 我们确定了每个 TTSS 的几个效应器，并发现两个 TTSS 表现出。明显的效应器特异性。