Chronic pulmonary infection caused by Pseudomonas aeruginosa is ultimately responsible for respiratory failure and death in most patients with cystic fibrosis. This unusual association between a specific microorganism and a genetic disease has not been explained on a molecular level. The pathogenesis of this infection must require elements unique both to the pathogen and the host. Genetic and biochemical techniques will be used to identify adhesins which are involved in the colonization of the CF and normal respiratory tract. Using gene replacement techniques, strains with mutations in genes involved in attachment will be constructed to identify and evaluate the roles of specific genetic elements in colonization. The receptors associated with these adhesins will be characterized and their location on the epithelial cell surface or in secreted high molecular weight glycoproteins will be established. These studies should provide a direct comparison between the receptors available for Pseudomonas binding to normal and CF epithelial cells in culture. The colonization process for many human pathogens requires the coordinate expression of several genes in response to a specific environmental stimulus. In the CF lung environmental factors such as increased osmolarity which are a direct consequence of aberrant chloride channel function in CF will be tested for their effect in stimulating the expression of genes required for colonization.