A diarrheal pathogen, enteropathogenic Escherichia coli (EPEC), triggers a flux of inositol phosphates in infected epithelial cells.

Abstract

SummaryEnteropathogenic Escherichia coli (EPEC) is a bacterial pathogen that causes diarrhea in infants by adhering to intestinal epithelial cells. EPEC induces host cell protein phosphorylation and increases intraceUular calcium levels that may function to initiate cytoskeletal rearrangement. We found that EPEC triggers the release of inositol phosphates (IPs) after adherence of bacteria to cultured epithelial cells. We also demonstrated that the EPEC-induced flux of IPs precedes actin rearrangement and bacterial invasion. EPEC mutants and tyrosine protein kinase inhibitors were used to establish that formation of IPs is dependent on tyrosine phosphorylation of a 90-kD HeLa protein. Collectively these results suggest that EPEC-induced tyrosine phosphorylation of a host cell substrate(s) leads to release of IPs, which may then trigger cytoskeletal rearrangement.

Role of Internalization in the Pathogenicity of Shiga Toxin‐Producing Escherichia coli Infection in a Gnotobiotic Murine Model

“…Indeed, the amount of Stx, whose level in the serum is considered to be directly involved in cases of death by STEC infection (17), markedly decreased when the host is treated with LAB or IgY that can inhibit the internalization of STEC, although the Stx level in the colon did not substantially change. The A/E phenomenon has been proven to stimulate the cells to induce activating signals including calcium and inositol phosphate fluxes, and tyrosine phosphorylation (7,13). It is therefore also possible that the change in the colonic epithelial cells induced by those activating signals facilitates the transmission of pathogenic bacterial products through the colon.…”

Identification of the intimin-binding domain of Tir of enteropathogenic Escherichia coli

“…Initially, bacteria adhere to the cell membrane in microcolonies by a process called localized adherence, mediated by the plasmidencoded bundle-forming pilus (BFP) (Giron et al, 1991). In the second step, there is effacement of the microvilli, and several signal transduction pathways are activated in the host cell, including release of IP3 and phosphorylation of proteins (Rosenshine et al, 1992;Foubister et al, 1994). During this stage, the bacteria translocate a protein called Tir (for translocated intimin receptor) to the mammalian cell membrane, where it acts as the receptor for EPEC's adhesion molecule intimin (Kenny et al, 1997a).…”

Enteropathogenic E. coli Interactions with Host Cells

“…When EPEC interact with cultured epithelial cells, several signal transduction pathways are activated in the epithelial cells, including the release of the eukaryotic secondary messengers, IP3, and intracellular calcium (5,9). EPEC binding to cultured epithelial cells also causes tyrosine phosphorylation of a 90 kDa protein found in the membranes of epithelial cells, Tir (formerly Hp90), which is not phosphorylated in uninfected cultured cells (16,17).…”

“…Addition of tyrosine kinase inhibitors inhibit the phosphorylation of Hp90 and EPEC uptake into epithelial cells. It appears that Tir phosphorylation precedes IP3 fluxes and cytoskeletal rearrangements (9). A second wave of signals occur as intimin (see below) mediates intimate adherence to host cells (13).…”