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Infection and Immunity, June 2000, p. 3108-3115, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Enterohemorrhagic Escherichia coli Induces Apoptosis Which Augments Bacterial Binding and Phosphatidylethanolamine Exposure on the Plasma Membrane Outer Leaflet

Debora Barnett Foster,1,2,* Maan Abul-Milh,1,2 Mario Huesca,3 and Clifford A. Lingwood2,4,5

Department of Chemistry, Biology and Chemical Engineering, Ryerson Polytechnic University,1 Departments of Biochemistry4 and Laboratory Medicine and Pathobiology,5 University of Toronto, Department of Microbiology, Sunnybrook Health Sciences Center,3 and Division of Infection, Injury, Immunity and Repair, Research Institute, Hospital for Sick Children,2 Toronto, Ontario, Canada

Received 12 October 1999/Returned for modification 21 December 1999/Accepted 8 February 2000

Enterohemorrhagic Escherichia coli (EHEC) is a gastrointestinal pathogen that causes watery diarrhea and hemorrhagic colitis and can lead to serious and even fatal complications such as hemolytic uremic syndrome. We investigated the ability of EHEC to kill host cells using three human epithelial cell lines. Analysis of phosphatidylserine expression, internucleosomal cleavage of host cell DNA and morphological changes detected by electron microscopy changes revealed evidence of apoptotic cell death. The rates and extents of cell death were similar for both verotoxin-producing and nonproducing strains of EHEC as well as for a related gastrointestinal pathogen, enteropathogenic 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 phosphatidylethanolamine, previously reported to bind EHEC and EPEC, was also increased on apoptotic cells but with little correlation to phosphatidylserine expression. Phosphatidylethanolamine levels but not phosphatidylserine levels on dying cells correlated with EHEC binding. Cells treated with phosphatidylethanolamine-containing liposomes also showed increased EHEC binding. These results suggest that bacterial induction of apoptosis offers an advantage for bacterial attachment by augmenting outer leaflet levels of the phosphatidylethanolamine receptor.

* Corresponding author. Mailing address: Department of Chemistry, Biology and Chemical Engineering, Ryerson Polytechnic University, 350 Victoria St., Toronto, Ontario, Canada M5B 2K3. Phone: (416) 979-5000, ext. 6345. Fax: (416) 979-5044. E-mail: dfoster{at}acs.ryerson.ca.

Infection and Immunity, June 2000, p. 3108-3115, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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