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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Cell Physiology |
| Volume | 301 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 2011 |
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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 journal › Article
}
TY - JOUR
T1 - Enterohemorrhagic escherichia coli infection stimulates shiga toxin 1 macropinocytosis and transcytosis across intestinal epithelial cells
AU - Lukyanenko, Valeriy
AU - Malyukova, Irina
AU - Hubbard, Ann Louise
AU - Delannoy, Michael
AU - Boedeker, Edgar
AU - Zhu, Chengru
AU - Cebotaru, Liudmila
AU - Kovbasnjuk, Olga N
PY - 2011/11
Y1 - 2011/11
N2 - 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.
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.
KW - Diarrhea
KW - Foodborne pathogens
KW - Transcytosis
UR - http://www.scopus.com/inward/record.url?scp=80054883703&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054883703&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.00036.2011
DO - 10.1152/ajpcell.00036.2011
M3 - Article
VL - 301
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 5
ER -