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Infect. Immun. doi:10.1128/IAI.01515-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Pet, a Non-AB Toxin, is Retrograde Transported and Translocated into Epithelial Cells

Department of Cell Biology, Centro de Investigación y de Estudios Avanzados (Cinvestav-Zacatenco), Ap. Postal 14-740, 07000 México, DF, Mexico;, Biomolecular Science Center and Department of Molecular Biology and Microbiology, University of Central Florida, 12722 Research Parkway, Orlando, Florida 32826

^* To whom correspondence should be addressed. Email: fnavarro{at}cell.cinvestav.mx.

	Abstract

The plasmid-encoded toxin (Pet) of enteroaggregative Escherichia coli is a 104 kDa autotransporter protein that exhibits proteolytic activity against the actin-binding protein -fodrin. Intracellular cleavage of epithelial fodrin by Pet disrupts the actin cytoskeleton, causing both cytotoxic and enterotoxic effects. Intoxication requires the serine protease activity of Pet and toxin endocytosis from clathrin-coated pits. Additional events in the intracellular trafficking of Pet are largely uncharacterized. Here, we show by confocal microscopy that internalized Pet is transferred from the early endosomes to the Golgi apparatus and then travels to the endoplasmic reticulum (ER). Pet associates with the Sec61p translocon before moving into the cytosol as an intact, 104 kDa protein. This translocation event contrasts with the export of other ER-translocating toxins in which only the catalytic A subunit of the AB toxin enters the cytosol. However, like these AB toxins, Pet intoxication was inhibited in a subset of mutant CHO cell lines with aberrant activity in the ER-associated degradation pathway of ER-to-cytosol translocation. This is the first report to document the cell surface-to-ER and ER-to-cytosol trafficking of a bacterial non-AB toxin.

This article has been cited by other articles:

• Navarro-Garcia, F., Canizalez-Roman, A., Vidal, J. E., Salazar, Ma. I. (2007). Intoxication of epithelial cells by plasmid-encoded toxin requires clathrin-mediated endocytosis. Microbiology 153: 2828-2838 [Abstract] [Full Text]