| Co-Investigator(Kenkyū-buntansha) |
TOMITA Toshio THE UNIVERISITY OF TOKYO,INSTITUTE OF MEDICAL SCIENCE,INSTRUCTOR, 医科学研究所, 講師 (00126129)
TOBE Toru THE UNIVERSITY OF TOKYO,INSTITUTE OF MEDICAL SCIENCE,RESEARCH ASSOCIATE, 医科学研究所, 助手 (70207596)
|
|---|
| Research Abstract |
Shigellae are the causative agents of bacillalry dysentery, a desease provoking sever bloody diarrhea in humans and monkeys. The most erucial step in the pathogenesis of shigellosis is invasiveness of shigellae into the intestinal epithlial cells, which requires the large-plasmid-encoded proteins, lpaB,lpaC and lpaD,although the exact mechanisms of the invasion of the epithelial cells by shigellae remained largely unclear. In this project, in order to get more insight into the molucluar mechanisms of the shigellae invasion, we undertook three studies ; the first was elucidation of biological activities of the lpa proteins to interact with the host cells. The second was to understand the mechanisms underlying thelpa export system. The last was investigation of the mechanisms on the temperature-regualted ipaBCD expression. The results obtained from these studies are summirized as follows ; (1) Release of lpa proteins from the cell surface is essential attribute for eliciting the invasiveness. (2) The release of lpa can be induced upon contact with epithelial cells. (3) The lpa release can also be triggered by contact with extracellular matrix, such as fibronectin, laminine or collagen IV.(4) Spa32, one of the Spa proteins, encoded by the large plasmid is required for the lpa release. (5) The released lpaB and lpaC form complexes, and the complex together with lpaD can bind to some component of the host cells. (6) The secretion of lpa onto the cell surface require functions encoded by mxi and spa operons. (7) The spa operon possesses eight spa genes. (8) The Spa homologs exist among various pathogenic bacteria as proteins mediating protein export. (9) The protein export system with Spa is a novel one, distinct from knwon secretion systems depending upon Sec or hemolysin protein export systems. (10) The thermosensitive expression of ipaBCD is gorverned by virB gene at the transcriptional level.
|
