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

在这项研究中，我们根据其基因组序列对三种重要致病细菌的发病机理和基因组多样性进行了全面分析，并在重大发现后获得了1。致病性大肠杆菌：（1）基于O157 Sakai序列，我们开发了○微阵列和整个基因组PCR扫描方法。（2）通过使用这两种方法，我们对O157和非O157肠肠肠肠球大肠杆菌（EHEC）菌株进行了大规模的基因组比较，并透露，在O157菌株中出现了显着的基因组多样性，并且具有预测性的变化，并且是这种基因的主要因素，是这种基因的多样性。此外，我们揭示了非O157 EHEC菌株包含大量O157中不存在的DNA。（3）我们发现RCSCDB两个组件调节系统和碳酸氢盐 - 感应系统控制病毒基因表达，并发现了这些调节中涉及的新型调节剂GRVA和PCH……通过使用微阵列表达Anakyses来表达ANAKYSES，更多的离子系统。这提供了第一条线索，以了解如何将病毒大肠杆菌的病毒基因表达系统纳入大肠杆菌的内在调节网络。（4）通过采用蛋白质组学方法，我们发现了O157.2的III型分泌系统（TTSS）的许多新效果。灌注梭状芽胞杆菌：（1）确定菌株13的基因组序列。（2）通过使用基于其基因组序列构建的微阵列，我们确定了141个基因，这些基因由ViRR/S两个组件调节系统或VIRR/S-VR-RNA系统控制。它们不仅包括病毒基因，还包括许多用于产生能量的基因和代谢，表明宿主组织中的病毒和生长基因受VIRR/S-VR-RNA系统的协调调节。（3）通过搜索VIRR结合序列，我们确定了两个新型的调节RNA.3。弧菌偏溶血：（1）确定菌株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TTSS1参与细胞毒性和TTSS2的腹泻性。（3）我们确定了每个TTS的几种效果，发现两个TTS的暴露了不同的效应子特异性。较少的