Enteropathogenic E. coli-induced barrier function alteration is not a consequence of host cell apoptosis.
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.
Viswanathan
V K
VK
Department of Medicine, Section of Digestive Diseases and Nutrition, University of Illinois at Chicago, Chicago, IL 60612-7323, USA.
Weflen
Andrew
A
Koutsouris
Athanasia
A
Roxas
Jennifer L
JL
Hecht
Gail
G
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D019943:Amino Acid Substitution; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D017097:Electric Impedance; D054308:Enteropathogenic Escherichia coli / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010539:Permeability / Q000187:drug effects; D021381:Protein Transport / Q000502:physiology; D011804:Quinolines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis; D019108:Tight Junctions / Q000382:microbiology / Q000502:physiology*
D000590:Amino Acid Chloromethyl Ketones; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D029968:Escherichia coli Proteins; C489109:EspFU protein, E coli; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D011804:Quinolines; D011994:Recombinant Proteins; C468548:quinoline-val-asp(OMe)-CH2-OPH