Two-partner secretion in Gram-negative bacteria: a thrifty, specific pathway for large virulence proteins

A collection of large virulence exoproteins, including Ca2+-independent cyt olysins, an iron acquisition protein and several adhesins, are secreted by the two-partner secretion (TPS) pathway in various Gram-negative bacteria. The hallmarks of the TPS pathway are the presence of an N-proximal module c alled the 'secretion domain' in the exoproteins that we have named the TpsA family, and the channel-forming beta -barrel transporter proteins we refer to as the TpsB family. The genes for cognate exoprotein and transporter pr otein are usually organized in an operon, Specific secretion signals are pr esent in a highly conserved region of the secretion domain of TpsAs. TpsBs probably serve as specific receptors of the TpsA secretion signals and as c hannels for the translocation of the exoproteins across the outer membrane. A subfamily of transporters also mediates activation of their cognate cyto lysins upon secretion. The exoproteins are synthesized as precursors with a n N-terminal cleavable signal peptide, and a subset of them carries an exte nded signal peptide of unknown function. According to our current model, th e exoproteins are probably translocated across the cytoplasmic membrane in a Sec-dependent fashion, and their signal peptide is probably processed by a LepB-type signal peptidase, The N-proximal secretion domain directs the e xoproteins towards their trans; porters early, so that translocation across both membranes is coupled. The exoproteins transit through the periplasm i n an extended conformation and fold progressively at the cell surface befor e eventually being released into-the extracellular milieu. Several adhesins also undergo extensive proteolytic processing upon secretion. The genes of many new TpsAs and TpsBs are found in recently sequenced genomes, suggesti ng that the TPS pathway is widespread.