Enterohemorrhagic Escherichia coli induces apoptosis which augments bacterial binding and phosphatidylethanolamine exposure on the plasma membrane outer leaflet

Enterohemorrhagic Escherichia coti (EHEC) is a gastrointestinal pathogen th at causes watery diarrhea and hemorrhagic colitis and can lead to serious a nd even fatal complications such as hemolytic uremic syndrome. We investiga ted the ability of EHEC to kill host cells using three human epithelial cel l lines, Analysis of phosphatidylserine expression, internucleosomal cleava ge of host cell DNA and morphological changes detected by electron microsco py changes revealed evidence of apoptotic cell death. The rates and extents of cell death were similar for both verotoxin-producing and nonproducing s trains of EHEC as well as for a related gastrointestinal pathogen, enteropa thogenic E. coli (EPEC). The induction of apoptosis by bacterial attachment was independent of verotoxin production and greater than that produced by a similar treatment with verotoxin alone. Expression of phosphatidylethanol amine, previously reported to bind EHEC and EPEC, was also increased on apo ptotic cells but with little correlation to phosphatidylserine expression. Phosphatidylethanolamine levels but not phosphatidylserine levels on dying cells correlated with EHEC binding. Cells treated with phosphatidylethanola mine-containing liposomes also showed increased EHEC binding. These results suggest that bacterial induction of apoptosis offers an advantage for bact erial attachment by augmenting outer leaflet levels of the phosphatidyletha nolamine receptor.