The proposed research focuses on the structural and functional organization of the cell surface of Escherichia coli and Salmonella species; special emphasis is placed on the characterization of interactions between virus particles and the host cell surface. We had previously shown that the surface of the growing bacterium is composed of a mosaic of structurally distinct domains of localized adhesions between cell wall and inner membrane. At these "adhesion sites", newly synthesized lipopolysaccharides and capsular polysaccharides are exported, F pili and flagellae are anchored and many additional functions involving specific target and receptor proteins appear also to be localized at these sites; furthermore, adhesion areas provide the injection sites for bacteriophages. We hypothesize that such clustering of functions enables the adhesion sites to control cell growth by quickly responding to physico-chemical alterations in the balanced state between cell and environment. A membrane response initiated over the adhesion sites seems to spread very fast over the entire cell surface. We propose to study: a) the kinetics of virus attachment and early events of receptor recognition by the virion; b) the interaction of virus capsids with cell surface during penetration of the cell coat; c) the speed of spreading of the cell surface signal; and d) we intend to isolate and characterize the membrane fractions containing adhesion sites. Well-suited for these projects is the polysaccharide capsule of Escherichia coli, which shields the bacterium from attack by most viruses and from recognition by macrophages; it can be isolated, purified and crystallized. Our studies will employ a combination of biophysical, virological and immunological methods; part of the project will be done in collaboration with other laboratories to optimize our data interpretation. It is hoped that the proposed research will aid us in an increased understanding of: a) the early effects of drugs and virus capsids on the cell coat, and b) of the integrated action of multiple discrete domains comprising the functional surface mosaic of a growing bacterium.