WELSH CT, SUMMERSGILL JT, MILLER RD; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. B-1378.
Department of Microbiology and Immunology and Division of Infectious Diseases, University of Louisville, Louisville, KY
The intracellular pathogen Legionella pneumophila is capable of survival within the phagosome due to an ability to inhibit phagolysosome formation. To date, the biochemical events that account for this inhibition have not been reported. The purpose of this project was to examine the effects of L.pneumophila on host cell signaling, focusing on the MAPK cascade. The procedures used human monocytes inoculated at an MOI of 10 with L.pneumophila strain AA100 (wild type), L.pneumophila strain GL-10 (DotA mutant), or an Escherichia coli control. After inoculation the tissue culture plates were centrifuged at 4 degreesC in order to synchronize ``phagocytic events. 30 and 60 min after the initiation of phagocytosis, the cells were lysed. Western Blotting was performed on the lysates with antibodies specific for the phosphorylated (active) state of MEK, ERK1/2, plus beta-actin. The results indicated that at 30 min MEK 1/2 and ERK 1/2 activation for AA100 (wt) were not significantly different from that of the GL-10 (mut) or the E.coli control. In contrast, by 60 min significant signaling differences were evident. Both Legionella strains exhibited a 2-fold increase in MEK activation over the E.coli control, while ERK 1/2 activation was approximately 40-45% less than the E.coli control and the GL-10 mutant. This leads to the conclusion that L.pneumophila AA100 (wt) is responsible for aberrant signaling that allows for the activation of MEK at greater levels than the control and interferes with the subsequent activation of ERK. The significance of this finding may help to explain how L.pneumophila can alter phagocytic function and promote intracellular survival.
Publication Types:
Keywords:
- Antigens, Bacterial
- Humans
- Legionella
- Legionella pneumophila
- MAP Kinase Signaling System
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinases
- Monocytes
- Phagocytosis
- Phagosomes
- Signal Transduction
- Vacuoles
- enzymology
- immunology
- metabolism
Other ID:
UI: 102269527
From Meeting Abstracts