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Induction of Increased Permeability of Polarized Enterocyte Monolayers by Enterotoxigenic Escherichia coli Heat-Labile Enterotoxin

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  • Division of Gastroenterology and Hepatology, Department of Medicine, Department of Microbiology and Immunology, and Center for Vaccine Development, Departments of Pediatrics and Medicine, University of Maryland School of Medicine, Baltimore, Maryland; Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, Louisiana

Enterotoxigenic Escherichia coli (ETEC) is a common cause of acute diarrhea in resource-poor settings. We report that some ETEC strains elicit a reduction in trans-epithelial electrical resistance (TER) in polarized T84 epithelial cell monolayers. The effect was irreversible up to 48 hours after a three-hour infection and was observed with heat-labile enterotoxin (LT)–producing strains, but not with heat-stable enterotoxin (ST)–producing strains. Using purified LT, a mutant with reduced ADP-ribosylating activity, and the LT-B subunit alone, we demonstrate that TER reduction requires a functional enterotoxin. Treatment of monolayers with LT or LT-producing strains of ETEC increases paracellular permeability to fluorescein isothiocyanate–dextran. Our data suggest that LT-producing ETEC strains may induce intestinal barrier dysfunction.

Author Notes

*Address correspondence to James P. Nataro, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA 22908. E-mail: jpn2r@virginia.edu†These authors contributed equally to this article.

Financial support: This study was supported by grant AI33096 from the National Institutes of Health to Joseph P. Nataro.

Authors' addresses: Roderick B. Kreisberg, Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, E-mail: rkrei001@yahoo.com. Jill Harper, Maura C. Strauman, and Mark Marohn, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, E-mails: jharper@medicine.mumaryland.edu, mstrauman@wistar.org, and mmaro001@umaryland.edu. John D. Clements, Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, LA, E-mail: jclemen@tulane.edu. James P. Nataro, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, E-mail: jpn2r@virginia.edu.

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