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Abstract

The invention provides methods of screening for modulators of microbial PA-I lectin/adhesin activity, including modulators of PA-I expression, as well as the modulators so identified, pharmaceutical compositions and kits containing such modulators. These modulators include soluble and membrane-bound bacterial signaling compounds produced by cells of a host containing a microbial pathogen. Methods for preventing and treating cell disorders, such as epithelial cell disorders including gut-derived sepsis, a burn injury, neonatal necrotizing enterocolitis, severe neutropenia, toxic colitis, inflammatory bowel disease, enteropathy, transplant rejection, pouchitis, pig belly, Pseudomonas-mediated opthalmologic infection, Pseudomonas-mediated otologic infection and Pseudomonas-mediated cutaneous infection, using the modulators are contemplated, as are methods for ameliorating a symptom associated with such a disorder. The invention further provides methods of treating or preventing disorders of the lung, including disorders affecting endothelial or epithelial cell barrier function, such as acute respiratory distress syndrome or pulmonary edema, as well as methods of preventing such disorders, and the above-named disorders, such as neonatal necrotizing enterocolitis, by administering a high molecular weight polyethylene glycol-like compound. Related methods of ameliorating a symptom associated with one of these disorders is also contemplated.

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