Yersinia enterocolitica, like many other enteric bacterial pathogens, demonstrates the capability for adherence to and penetration of epithelial cells in in vitro cultures. This ability is restricted to strains of Y. enterocolitica that are recognizable in other respects as pathogenic for man; consequently, it is a basic requisite and indicator of virulence. Epithelial cell adherence-penetration by Y. enterocolitica appears to be unique in many aspects from other Enterobacteriaceae that demonstrate this ability, particularly in that the process is not mediated by fimbriae. This research project is concerned with the following aspects of adherence-penetration of epithelial cells by Y. enterocolitica: (i) Improvement of the system for observing bacterial-epithelial cell interactions in a way that will provide a quantitative model permitting kinetic description of the process. (ii) Identification of in vitro conditions necessary for optimum epithelial cell adherence-penetraion including those relating to the bacterium and those to the system provided for bacterial-epithelial cell interaction. (iii) Evaluation of the relative role of bacterial and host cell metabolic-enzymatic activity and surface structure integrity in adherence through studies on the influence of physical agents, metabolic inhibitors and structure modifiers. (iv) Identification of inhibitors of adherence that are likely to represent receptor or adhesin analogues. (v) Comparison of surface polysaccharide, protein and lipopolysaccharide patterns in a mutant that has lost adherence-penetration capability with those of the parent strain. (vi) Separation of chemical components from the bacterial outer membrane and evaluation of their role in epithelial cell adherence-penetration. (vii) Development of an immunodiagnostic test procedure for identification of pathogenic strains based on a common antigen involved in epithelial cell adherence-penetration. (viii) Evaluation of the activity of inhibitors of adherence-penetration in an in vivo model.
