Inhibition of attaching and effacing lesion formation following enteropathogenic Escherichia coli and Shiga toxin-producing E. coli infection.
Enteropathogenic Escherichia coli (EPEC) and Shiga toxin-producing E. coli (STEC) induce cytoskeletal changes in infected epithelial cells. To further characterize host cytosolic responses to infection, a series of specific cell-signaling inhibitors were employed. Initial bacterial adhesion to HEp-2 epithelial cells was not reduced, whereas alpha-actinin accumulation in infected cells was blocked by a phosphoinositide-specific phospholipase C inhibitor (ET-18-OCH3), phosphoinositide 3-kinase inhibitors (wortmannin and LY294002), and a 5-lipoxygenase inhibitor, nordihydroguaretic acid. A cyclooxygenase-2 inhibitor (NS-398), however, did not block alpha-actinin reorganization in response to EPEC and STEC infections. Understanding signal transduction responses to enteric pathogens could provide the basis for the development of novel therapeutic strategies.
Johnson-Henry
K
K
Research Institute, Hospital for Sick Children, Departments of Paediatrics and Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Wallace
J L
JL
Basappa
N S
NS
Soni
R
R
Wu
G K
GK
Sherman
P M
PM
D000185:Actinin / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol / Q000494:pharmacology; D008565:Membrane Proteins; D009025:Morpholines / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010742:Phospholipid Ethers / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D022621:Shiga Toxin; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D009025:Morpholines; D009578:Nitrobenzenes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010742:Phospholipid Ethers; D013449:Sulfonamides; D000185:Actinin; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C026659:edelfosine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D022621:Shiga Toxin; D009637:Masoprocol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010738:Type C Phospholipases; D000077191:Wortmannin