Enteropathogenic Escherichia coli infection triggers host phospholipid metabolism perturbations.
Enteropathogenic Escherichia coli (EPEC) specifically recognizes phosphatidylethanolamine (PE) on the outer leaflet of host epithelial cells. EPEC also induces apoptosis in epithelial cells, which results in increased levels of outer leaflet PE and increased bacterial binding. Consequently, it is of interest to investigate whether EPEC infection perturbs host cell phospholipid metabolism and whether the changes play a role in the apoptotic signaling. Our findings indicate that EPEC infection results in a significant increase in the epithelial cell PE level and a corresponding decrease in the phosphatidylcholine (PC) level. PE synthesis via both the de novo pathway and the serine decarboxylation pathway was enhanced, and de novo synthesis of phosphatidylcholine via CDP-choline was reduced. The changes were transitory, and the maximum change was noted after 4 to 5 h of infection. Addition of exogenous PC or CDP-choline to epithelial cells prior to infection abrogated EPEC-induced apoptosis, suggesting that EPEC infection inhibits the CTP-phosphocholine cytidylyltransferase step in PC synthesis, which is reportedly inhibited during nonmicrobially induced apoptosis. On the other hand, incorporation of exogenous PE by the host cells enhanced EPEC-induced apoptosis and necrosis without increasing bacterial adhesion. This is the first report that pathogen-induced apoptosis is associated with significant changes in PE and PC metabolism, and the results suggest that EPEC adhesion to a host membrane phospholipid plays a role in disruption of host phospholipid metabolism.
Wu
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Y
Department of Chemistry and Biology, Ryerson University, 350 Victoria Street, Toronto, Ontario, Canada M5B 2K3.
Lau
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B
Smith
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Troyan
K
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Barnett Foster
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DE
D017209:Apoptosis; D002478:Cells, Cultured; D003566:Cytidine Diphosphate Choline; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000472:pathogenicity*; D010861:Fimbriae, Bacterial / Q000502:physiology; D009336:Necrosis; D010713:Phosphatidylcholines / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*
D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D003566:Cytidine Diphosphate Choline