PROTEIN SECRETION BY ENTEROPATHOGENIC ESCHERICHIA-COLI IS ESSENTIAL FOR TRANSDUCING SIGNALS TO EPITHELIAL-CELLS

Enteropathogenic Escherichia coli (EPEC), a major cause of pediatric d iarrhea, adheres to epithelial cells and activates host cell signal tr ansduction pathways. We have identified five proteins that are secrete d by EPEC and show that this secretion process is critical for trigger ing signal transduction events in epithelial cells. Protein secretion occurs via two pathways: one secretes a 110-kDa protein and the other mediates export of the four remaining proteins. Secretion of all five proteins was regulated by temperature and the perA locus, two factors which regulate expression of other known EPEC virulence factors. Amino -terminal sequence analysis of the secreted polypeptides identified on e protein (37 kDa) as the product of the eaeB gene, a genetic locus pr eviously shown to be necessary for signal transduction. A second prote in (39 kDa) showed significant homology with glyceraldehyde-3-phosphat e dehydrogenase, while the other three proteins (110, 40, and 25 kDa) were unique. The secreted proteins associated with epithelial cells, a nd EaeB became resistant to protease digestion upon association, sugge sting that intimate interactions are required for transducing signals.