PATHOGENIC NEISSERIAE - INTERPLAY BETWEEN PRO-EUKARYOTIC AND EUKARYOTIC WORLDS

The pathogenic Neisseria species constitute a multi-faceted infection model of a highly adapted pathogen-host relationship. Several bacteria l and host-cell factors involved in the cellular cross-talk have been recently unraveled. Using Neisseria gonorrhoeae as a prototype, severa l structurally variable surface proteins, including pill and Opa prote ins, have been revealed as adhesins recognizing distinct host-cell rec eptors. The Opa proteins, in particular, are important in facilitating interaction with heparan sulfate proteoglycan receptors and members o f the CD66 and integrin receptor families. These interactions not only enable the pathogens' anchoring, and penetration into, the human muco sa but also stimulate cellular signaling cascades involving the phosph atidylcholine-dependent phospholipase C, acidic sphingomyelinase and p rotein kinase C in epithelial cells, and Src-related kinases, Rad, p21 -activated kinase and Jun N-terminal kinase in phagocytic cells. Activ ation of these pathways is essential for the entry and intracellular a ccommodation of the pathogens but also leads to an early induction of cytokine release, thus priming the immune response. It is believed tha t detailed knowledge of cellular signaling cascades activated by infec tion will aid us in applying known and novel interfering drugs, in add ition to classical antibiotic therapy, to the therapeutic and prophyla ctic treatment of persistent or otherwise difficult-to-treat bacterial infections.