Enterohemorrhagic Escherichia coli infection stimulates Shiga toxin 1 macropinocytosis and transcytosis across intestinal epithelial cells.

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, antibiotic-independent strategy for prevention of the harmful consequences of enterohemorrhagic E. coli infection.

• Authors: Valeriy Lukyanenko, Irina Malyukova, Ann Hubbard, Michael Delannoy, Edgar Boedeker, Chengru Zhu, Liudmila Cebotaru, Olga Kovbasnjuk
• Journal: American journal of physiology. Cell physiology (Am J Physiol Cell Physiol) Vol. 301 Issue 5 Pg. C1140-9 (Nov 2011) ISSN: 1522-1563 [Electronic] United States
• PMID: 21832249 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Actins
• Shiga Toxin 1
• Myosin Type II
• cdc42 GTP-Binding Protein

Topics

• Actins (metabolism)
• Cell Line
• Colon (metabolism, microbiology)
• Enterohemorrhagic Escherichia coli
• Escherichia coli Infections (metabolism, microbiology)
• Humans
• Intestinal Mucosa (metabolism, microbiology)
• Myosin Type II (metabolism)
• Pinocytosis
• Shiga Toxin 1 (metabolism)
• Transcytosis
• cdc42 GTP-Binding Protein (metabolism)