Enterohemorrhagic escherichia coli infection stimulates shiga toxin 1 macropinocytosis and transcytosis across intestinal epithelial cells

Valeriy Lukyanenko, Irina Malyukova, Ann Louise Hubbard, Michael Delannoy, Edgar Boedeker, Chengru Zhu, Liudmila Cebotaru, Olga N Kovbasnjuk

Research output: Contribution to journalArticle

Abstract

Gastrointestinal infection with Shiga toxins producing enterohemorrhagic Escherichia coli causes the spectrum of gastrointestinal and systemic complications, including hemorrhagic colitis and hemolytic uremic syndrome, which is fatal in ~10% of patients. However, the molecular mechanisms of Stx endocytosis by enterocytes and the toxins cross the intestinal epithelium are largely uncharacterized. We have studied Shiga toxin 1 entry into enterohemorrhagic E. coli-infected intestinal epithelial cells and found that bacteria stimulate Shiga toxin 1 macropinocytosis through actin remodeling. This enterohemorrhagic E. coli-caused macropinocytosis occurs through a nonmuscle myosin II and cell division control 42 (Cdc42)-dependent mechanism. Macropinocytosis of Shiga toxin 1 is followed by its transcytosis to the basolateral environment, a step that is necessary for its systemic spread. Inhibition of Shiga toxin 1 macropinocytosis significantly decreases toxin uptake by intestinal epithelial cells and in this way provides an attractive, antibioticindependent strategy for prevention of the harmful consequences of enterohemorrhagic E. coli infection.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume301
Issue number5
DOIs
StatePublished - Nov 2011

Fingerprint

Shiga Toxin 1
Enterohemorrhagic Escherichia coli
Transcytosis
Escherichia coli Infections
Epithelial Cells
Myosin Type II
Shiga-Toxigenic Escherichia coli
Hemolytic-Uremic Syndrome
Enterocytes
Colitis
Intestinal Mucosa
Endocytosis
Cell Division
Actins
Bacteria
Infection

Keywords

  • Diarrhea
  • Foodborne pathogens
  • Transcytosis

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Enterohemorrhagic escherichia coli infection stimulates shiga toxin 1 macropinocytosis and transcytosis across intestinal epithelial cells. / Lukyanenko, Valeriy; Malyukova, Irina; Hubbard, Ann Louise; Delannoy, Michael; Boedeker, Edgar; Zhu, Chengru; Cebotaru, Liudmila; Kovbasnjuk, Olga N.

In: American Journal of Physiology - Cell Physiology, Vol. 301, No. 5, 11.2011.

Research output: Contribution to journalArticle

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AU - Lukyanenko, Valeriy

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AU - Hubbard, Ann Louise

AU - Delannoy, Michael

AU - Boedeker, Edgar

AU - Zhu, Chengru

AU - Cebotaru, Liudmila

AU - Kovbasnjuk, Olga N

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AB - Gastrointestinal infection with Shiga toxins producing enterohemorrhagic Escherichia coli causes the spectrum of gastrointestinal and systemic complications, including hemorrhagic colitis and hemolytic uremic syndrome, which is fatal in ~10% of patients. However, the molecular mechanisms of Stx endocytosis by enterocytes and the toxins cross the intestinal epithelium are largely uncharacterized. We have studied Shiga toxin 1 entry into enterohemorrhagic E. coli-infected intestinal epithelial cells and found that bacteria stimulate Shiga toxin 1 macropinocytosis through actin remodeling. This enterohemorrhagic E. coli-caused macropinocytosis occurs through a nonmuscle myosin II and cell division control 42 (Cdc42)-dependent mechanism. Macropinocytosis of Shiga toxin 1 is followed by its transcytosis to the basolateral environment, a step that is necessary for its systemic spread. Inhibition of Shiga toxin 1 macropinocytosis significantly decreases toxin uptake by intestinal epithelial cells and in this way provides an attractive, antibioticindependent strategy for prevention of the harmful consequences of enterohemorrhagic E. coli infection.

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