Project/Area Number |
14014241
|
Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
|
Research Institution | University of Miyazaki (2004) 宮崎医科大学 (2002-2003) |
Principal Investigator |
HAYASHI Tetsuya University of Miyazaki, Frontier Research Center, Professor, フロンティア科学実験総合センター, 教授 (10173014)
|
Co-Investigator(Kenkyū-buntansha) |
OGURA Yoshitoshi University of Miyazaki, Frontier Research Center, Joshu, フロンティア科学実験総合センター, 助手 (40363585)
OOKA Tadasuke University of Miyazaki, Faculty of Medicine, Joshu, 医学部, 助手 (50363594)
TOBE Toru Osaka University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (70207596)
SHIMIZU Tohru Kanazawa University, Graduate School of Medical Science, Professor, 大学院医学研究科, 教授 (80235655)
IIDA Tetsuya Osaka University, Center for Infectious diseases, Associate Professor, 微生物病研究所, 助教授 (90221746)
中山 恵介 宮崎大学, 医学部, 助手 (10347057)
大西 真 宮崎医科大学, 医学部, 助教授 (10233214)
|
Project Period (FY) |
2002 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥70,500,000 (Direct Cost: ¥70,500,000)
Fiscal Year 2004: ¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 2003: ¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 2002: ¥22,500,000 (Direct Cost: ¥22,500,000)
|
Keywords | 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 |
Research Abstract |
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
|