Protein Secretion in Gram-Negative Bacteria

Since the initial characterization of the hemolysin secretion system (Hly) from the Gram-negative bacterium, E. coli, by W. Goebel’s group in the late 1970s, there has been a surprising proliferation of discoveries of distinct pro¬tein secretion mechanisms in many Gram-negative bacteria. Both for the Hly system and for other secretion pathways, developments have been the most dramatic over the last 5 years and, therefore, in this review we have placed most detailed emphasis upon this period up to approximately mid-1996. Previous reviews have generally agreed on the classification of secretion Types I, II, III, indicated in this review. Here (see also reference 5), we have proposed a classification for additional pathways: Type IV (auto-transporter systems like the IgA pathway); Type V for surface pilins (E. coli Pap system), the functionally related Type Va, although not homologous with the pilin system, are transported from the periplasm via a single outer membrane “translocator” protein; Type VI for the special case of the filamentous phage (nucleo-protein) secretory pathway. The secretion of flagellar proteins on to the cell surface, although not discussed in this review, could be considered yet another pathway (for review see reference 5a). However, the biogenesis of the flagellum involves at least eight proteins with homology to proteins of the Type III pathway. We emphasize that Types IV–VI, as defined here, are useful working classifications but a generally agreed classification for these secretion pathways in the literature has not yet emerged. What can be generally agreed upon is that Types I, III and VI are one step processes with translocation from cytoplasm directly on to the cell surface or to the medium, while other pathways employ a two-step mechanism involving initial export to the periplasm targeted by an N-terminal signal via the Sec-machinery (general export pathway). The second stage then involves translocation across the outer membrane by various mechanisms. Importantly, the proteins of the latter group are apparently translocated across the outer membrane in a fully folded form, while proteins translocated directly to the outside of the cell (Types I, III) and perhaps IV may be required to re-fold on the surface.