Summary of Research Project Results under JSPS FY2001
"Research for the Future Program"

1.Research Institution The University of Tokyo
2.Research Area Life Sciences
3.Research Field Infections Diseases and Bioregulation
4.Term of Project FY 1997 〜 FY 2001
5.Project Number 97L00702
6.Title of Project Mechanisms of Epithelial Infection by Enteropathogenic Bacteria and its Application for Control

7.Project Leader
Name Institution,Department Title of Position
Chihiro Sasagawa The University of Tokyo, Institute of Medical Science Professor

8.Core Members

Names Institution,Department Title of Position
Toru Tobe University of Osaka, Graduate School of Medicine Associate Professor
Toshihiko Suzuki The University of Tokyo, Institute of Medical Science Lecturer
Ichiro Tatsuno The University of Tokyo, Institute of Medical Science ResearchAssociate

9.Summary of Research Results

The process of bacterial infection of mucosal barrier including the subsequent steps required for establishment of infectious diseases are quite complicated, dynamic biological events. Each infectious step is proceeded with the interaction between the pathogen and the host cells including the host cellular responses. In this research project, therefore, we have endeavored to elucidate bacterial adherence, intimate attachment, invasion and cell-cell spreading, sine they constitute of the essential early bacterial infectious step. We have studied the following bacterial infection events; (i) the mechanisms of invasion of mucosal barrier by Shigella including the cell-cell spreading, (ii) identification and characterization of virulence of enterohemorrhagic Escherichia coli (O157) and investigation of the intimate adherence mechanisms to the host cells, and (iii) the roles of bundle pili of enteropathogenic Escherichia coli (EPEC) in the initial adherence to the host cells. Accumulation of the knowledge on the bacterial infectious systems will be useful to develop new strategies required for preventing or controlling bacterial infection. The followings are the brief summary of our results gained by each study.
(i) Shigella direct its own internalization into macrophages by activating macrophage by delivered IpaC, while for invasion of epithelial cells, the role of VirA is important, since VirA can stimulate host Rac1 through induction of microtubule depolymerization. Shigella VirG, the essential protein for mediating actin-based motility can directly recruit N-WASP, thereby the bound Cdc42, profilin and Arp2/3 lead to actin polymerization at the vicinity of bacterial end.
(ii) The determination of O157 genomic sequence was undertaken by integrating our study on the virulence loci involved in bacterial attachment to epithelial cells. The attachment takes place through two-step processes mediated by the proteins encoded by LEE-genes including the other chromosomal loci and the 90-kb plasmid.
(iii) EPEC bundle-forming pili mediate not only for the initial bacterial attachment to the host cells, but also involves in determining the host specificity. EPEC possessed a 70-kb plasmid on which genes required for the biosynthesis of the pili and the regulatory elements are present.

10.Key Words

(1)pathogenic bacteria、(2)infection、(3)host response
(4)pathogenecity、(5)mucosal barrier、(6)pathogen
(7)infectious diseases、(8)effector、(9)cellular microbiology