Type V Secretion Systems: An Overview of Passenger Domain Functions

Abstract

Bacteria secrete proteins for different purposes such as communication, virulence functions, adhesion to surfaces, nutrient acquisition, or growth inhibition of competing bacteria. For secretion of proteins, Gram-negative bacteria have evolved different secretion systems, classified as secretion systems I through IX to date. While some of these systems consist of multiple proteins building a complex spanning the cell envelope, the type V secretion system, the subject of this review, is rather minimal. Proteins of the Type V secretion system are often called autotransporters (ATs). In the simplest case, a type V secretion system consists of only one polypeptide chain with a β-barrel translocator domain in the membrane, and an extracellular passenger or effector region. Depending on the exact domain architecture of the protein, type V secretion systems can be further separated into sub-groups termed type Va through e, and possibly another recently identified subtype termed Vf. While this classification works well when it comes to the architecture of the proteins, this is not the case for the function(s) of the secreted passenger. In this review, we will give an overview of the functions of the passengers of the different AT classes, shedding more light on the variety of functions carried out by type V secretion systems.

Keywords: AT; Gram-negative microorganisms; bacterial outer membrane; secretion systems; virulence.

FIGURE 1

Schematic of type V secretion system subclasses. β-barrels and POTRA domains are shown in blue, linkers and TPS domains in green, and passengers in orange. The periplasmic extension of type Ve proteins is in purple. The positions of the N- and C-termini are indicated. Type Vf is not fully established as part of the type V secretion scheme; this is denoted by the question mark.

FIGURE 2

Typical activities of autotransporter proteins. The major activities found in autotransporters are shown schematically. Green bacteria express autotransporters, but red bacteria do not. Autotransporters mediate activities such as adhesion to host cells or the extracellular matrix (ECM), invasion of host cells, immune evasion and serum resistance, contact-dependent growth inhibition, toxicity toward host cells, intracellular mobility, protease activity, and autoaggregation and biofilm formation. Cytolysin activity can be mediated by lipases or pore-forming toxins. Immune evasion can be accomplished by a variety of mechanisms, such as by binding to the constant regions of antibodies to prevent opsonisation (depicted here), cleavage of antibodies, mediating phagocytosis resistance or modulating immune cell signaling and gene regulation. In serum resistance, bacteria become resistant to the bactericidal effects of complement (shown as orange cylinders) by binding to complement-regulatory factors such as Factor H (shown as yellow ribbons). For full descriptions, see main text.