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 microM) or UO126 (100 microM), reduced P. aeruginosa invasion by approximately 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 microM), reduced P. aeruginosa invasion by approximately 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.
Evans
David J
DJ
Morton D. Sarver Laboratory for Cornea and Contact Lens Research, School of Optometry, University of California, Berkeley, CA 94720, USA.
Maltseva
Inna A
IA
Wu
Josephine
J
Fleiszig
Suzanne M J
SM
D000818:Animals; D002478:Cells, Cultured; D019573:Epithelium, Corneal / Q000382:microbiology* / Q000502:physiology; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000502:physiology*; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology*
D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases