Pseudomonas aeruginosa internalization by corneal epithelial cells involves MEK and ERK signal transduction proteins

Invasion of epithelial cells represents a potential pathogenic mechanism for Pseudomonas aeruginosa. We explored the role of mitogen-activated protein kinase kinases (MEK 1/2) and the extracellular signal-regulated kinases (ERK 1/2) in P. aeruginosa invasion. Treatment of corneal epithelial cells with MEK inhibitors, PD98059 (20 muM) or UO126 (100 muM), reduced P. aeruginosa invasion by similar to 60% without affecting bacterial association with the cells (P = 0.0001). UO124, a negative control for UO126, had no effect on bacterial internalization. Infection of cells with an internalization-defective flhA mutant of P. aeruginosa was associated with less ERK 1/2 tyrosine phosphorylation than infection with wild-type invasive P. aeruginosa. An ERK-2 inhibitor, 5-iodotubercidin (20 PM), reduced P. aeruginosa invasion by similar to 40% (P = 0.035). Together, these data suggest that P. aeruginosa internalization by epithelial cells involves a pathway(s) that includes MEK and ERK signaling proteins. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.