Enteropathogenic E. coli-induced barrier function alteration is not a consequence of host cell apoptosis

Virinchipuram Viswanathan, Andrew Weflen, Athanasia Koutsouris, Jennifer L. Roxas, Gail Hecht

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Enteropathogenic Escherichia coli (EPEC) is a diarrheagenic pathogen that perturbs intestinal epithelial function. Many of the alterations in the host cells are mediated by effector molecules that are secreted directly into epithelial cells by the EPEC type III secretion system. The secreted effector molecule EspF plays a key role in redistributing tight junction proteins and altering epithelial barrier function. EspF has also been shown to localize to mitochondria and trigger membrane depolarization and eventual host cell death. The relationship, if any, between EspF-induced host cell death and epithelial barrier disruption is presently not known. Site-directed mutation of leucine 16 (L16E) of EspF impairs both mitochondrial localization and consequent host cell death. Although the mutation lies within a region critical for type III secretion, EspF(L16E) is secreted efficiently from EPEC. Despite its inability to promote cell death, EspF(L16E) was not impaired for tight junction alteration or barrier disruption. Consistent with this, the pan-caspase inhibitor Q-VD-OPH, despite reducing EPEC-induced host cell death, had no effect on infection-mediated barrier function alteration. Thus EPEC alters the epithelial barrier independent of its ability to induce host cell death.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume294
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

Fingerprint

Enteropathogenic Escherichia coli
Cell Death
Apoptosis
Tight Junction Proteins
Mutation
Caspase Inhibitors
Tight Junctions
Leucine
Mitochondria
Epithelial Cells
Membranes
Infection

Keywords

  • EspF
  • Pathogenesis
  • Tight junction

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Enteropathogenic E. coli-induced barrier function alteration is not a consequence of host cell apoptosis. / Viswanathan, Virinchipuram; Weflen, Andrew; Koutsouris, Athanasia; Roxas, Jennifer L.; Hecht, Gail.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 294, No. 5, 05.2008.

Research output: Contribution to journalArticle

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