T5SS

T5SS, or Type V secretion system, is a group of protein export pathways found in many Gram-negative bacteria. Known for simplicity compared with other secretion systems, T5SS channels typically move virulence-associated proteins from the periplasm to the cell surface or extracellular space. The system is commonly referred to as autotransporters, because the secretion and translocation functions are carried out by components encoded within the same polypeptide or operon.

The Type V secretion system encompasses several subfamilies, with the main distinctions based on the organization of the transporter and passenger proteins. Classical autotransporters (T5aSS) consist of a single polypeptide that contains an N-terminal signal sequence for Sec-dependent translocation across the inner membrane, a passenger domain, and a C-terminal β-barrel domain that inserts into the outer membrane. The β-barrel forms a pore through which the passenger domain is translocated to the cell surface, and in many cases the passenger is released by autoproteolysis or remains surface-associated.

Two-partner secretion (TPS, or T5bSS) features separate polypeptides: a secreted passenger protein (the TpsA substrate) and a dedicated outer membrane transporter (the TpsB pore). The passenger is exported through the TpsB channel to the cell surface or extracellular milieu, often serving adhesion or enzymatic functions.

A third notable subgroup, trimeric autotransporters (T5cSS), assemble as trimers and use a shared β-barrel channel to export multiple passenger domains, forming multimeric adhesion and virulence factors.

T5SS proteins are widely distributed among pathogenic bacteria and contribute to adhesion, proteolysis, immune interaction, and biofilm formation. Notable examples include IgA proteases in Neisseria, YadA in Yersinia, and filamentous hemagglutinin components in Bordetella pertussis. The system remains a focus of study for understanding bacterial virulence and for developing therapeutic interventions.