We have previously shown that enterotoxigenic invasion protein A (Tia), a 25-kDa outer membrane protein encoded on an apparent pathogenicity island of enterotoxigenic Escherichia coli (ETEC) strain H10407, mediates attachment to and invasion into cultured human gastrointestinal epithelial cells. The epithelial cell receptor(s) for Tia has not been identified. Here we show that Tia interacts with cell surface heparan sulfate proteoglycans. Recombinant E. coli expressing Tia mediated invasion into wild-type epithelial cell lines but not invasion into proteoglycan-deficient cells. Furthermore, wild-type eukaryotic cells, but not proteoglycandeficient eukaryotic cells, attached to immobilized polyhistidine-tagged recombinant Tia (rTia). Binding of epithelial cells to immobilized rTia was inhibited by exogenous heparan sulfate glycosaminoglycans but not by hyaluronic acid, dermatan sulfate, or chondroitin sulfate. Similarly, pretreatment of eukaryotic cells with heparinase I, but not pretreatment of eukaryotic cells with chrondroitinase ABC, inhibited attachment to rTia. In addition, we also observed heparin binding to both immobilized rTia and recombinant E. coli expressing Tia. Heparin binding was inhibited by a synthetic peptide representing a surface loop of Tia, as well as by antibodies directed against this peptide. Additional studies indicated that Tia, as a prokaryotic heparin binding protein, may also interact via sulfated proteoglycan molecular bridges with a number of mammalian heparan sulfate binding proteins. These findings suggest that the binding of Tia to host epithelial cells is mediated at least in part through heparan sulfate proteoglycans and that ETEC belongs on the growing list of pathogens that utilize these ubiquitous cell surface molecules as receptors.Enterotoxigenic Escherichia coli (ETEC) strains remain a formidable cause of diarrheal disease and are a leading cause of infant mortality in developing countries. This heterogeneous group of pathogens, distinguished by their ability to cause diarrhea through the production of heat-labile and/or heatstable enterotoxins, collectively account for an estimated 200 million episodes of diarrheal illness and more than three-quarters of a million deaths annually (2). These organisms have occasionally been identified as the causes of food-borne outbreaks in industrialized countries (1, 41) and are still the most common cause of diarrhea in travelers (44).Colonization of the small intestine is a critical element in the pathogenesis of enterotoxigenic disease and is mediated, at least in part, by a heterogeneous group of antigenically distinct plasmid-encoded adhesins referred to as colonization factor antigens or coli surface antigens. At least 20 established or putative colonization factors have been identified in human ETEC strains to date (11). This heterogeneity has hampered ETEC vaccine development efforts. Previous studies have demonstrated that immunity directed against a single colonization factor antigen provides protection against strains expr...

The risk of the mobilization of coal ash into the environment has highlighted the need for the assessment of the environmental behavior of coal ash, particularly with respect to toxic trace elements such as arsenic (As). Here, we examined As speciation in coal fly ash samples and transformations in response to aquatic redox conditions. X-ray absorption spectroscopy indicated that 92-97% of total As occurred as As(V), with the remainder present as As(III). Major As-bearing hosts in unamended ashes were glass, iron (oxyhydr)oxides, and calcium arsenate. Oxic leaching resulted in immediate As mobilization to the aqueous phase, reprecipitation of As-iron ferrihydrite, and As adsorption to mineral surfaces. Under anoxic conditions, the (reductive) dissolution of As-bearing phases such as iron ferrihydrite resulted in increased dissolved As compared to oxic conditions and reprecipitation of iron arsenate. Overall, As in coal ash is not environmentally stable and can participate in local biogeochemical cycles.

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