The RTX toxin superfamily is a group of cytolysins and cytotoxins produced by bacteria. There are over 1000 known members with a variety of functions. The RTX family is defined by two common features: characteristic repeats in the toxin protein sequences, and extracellular secretion by the type I secretion systems (T1SS). The name RTX (repeats in toxin) refers to the glycine and aspartate-rich repeats located at the C-terminus of the toxin proteins, which facilitate export by a dedicated T1SS encoded within the rtx operon.
RTX proteins range from 40 to over 600 kDa in size and all contain C-terminally located glycine and aspartate-rich repeat sequences of nine amino acids. The repeats contain the common sequence structure [GGXGXDX[L/I/V/W/Y/F]X], (where X represents any amino acid), but the number of repeats varies within RTX protein family members. These consensus regions function as sites for Ca2+ binding, which facilitate folding of the RTX protein following export via an ATP-mediated type 1 secretion system (T1SS). Most of the T1SS proteins are encoded within the rtx operon. The T1SS proteins form a continuous channel spanning both the inner membrane (IM) and outer membrane (OM) of the bacterial cell, preventing RTX toxin exposure to the periplasmic space (between the IM and OM). Type 1 secretion system components include: an ABC transporter (TC# 3.A.1), a membrane fusion protein (MFP; TC# 8.A.1), and an outer membrane protein (OMF; TC# 1.B.17). The OMF is often encoded outside of the rtx operon as it may have multiple functions within the cell. In Escherichia coli, Pasteurella haemolytica, and Vibrio cholerae, TolC functions as the OMP in T1SS RTX toxin export. In each case, the tolC gene is located outside the rtx operon and encodes a conserved multifunctional protein. During transport, the T1SS recognizes the C-terminal repeats of the RTX toxin, and the C-terminus is transferred first through the channel.