The objectives of this proposal are to find means to alter host-cell responsiveness to the heat-labile enterotoxins of Vibrio cholerae and Escherichia coli by modulation of the receptors that bind the toxins. Similar to hormones and other ligand systems, exposure of target cells to these toxins or toxin derivatives lead to a down-regulation of toxin receptors and toxin binding. The aims of the proposal are to delineate the kinetics of these changes and to correlate them with changes in cellular responsiveness to the toxins. The relative contributions of specific and non-specific toxin binding in mediating the toxin's actions will also be examined. The effects of viral infection and alterations in cellular nutrition, as examples of environmental influences on host-cell responsiveness to toxin, will be studied. Finally, the contribution that bacterial adherence makes to cellular toxicity, and vice versa, will be explored, using genetically reconstructed mutants.