Adherence of bacteria to specific target tisues in the animal host is an important aspect of the pathogenesis of a variety of infectious diseases. In this research, we will analyze the factors which enable enteropathogenic Escherichia coli to adhere to the proximal small intestine of animals and man. This adherence is mediated by proteinaceous surface antigens. Several adherence antigens have been described; K88, K99, CF. Each antigen is specific for the colonization of a different animal species: K88, pigs; K99, calves and lambs; CF, humans. Our approach to this study is basd on the fact that the adherence antigens are carried on transmissible plasmids. We will study the individual plasmids which encode the K88, K99 and CF adherence antigens by isolation of each plasmid type as a single molecular entity in the well characterized E. coli K12 genetic background. Using recombinant DNA methodology, the antigen determinants will be isolated on small hybrid plasmids so that we may study the nature and control of the antigen gene products in more detail. The hybrid plasmids will also be used in DNA-DNA hybridization studies to assess the degree of relatedness among the determinants for antigens which are specific for different animal species. We will attempt to devise an in vitro system to assay specific adherence and determine the nature of the mammalian cell receptors and the basis of species specificity in adherence. It is hoped that this research will lead to a better understanding of the bacteria-host interactions involved in specific adherence and will contribute to the development of effective programs of immunoprophylaxis.