[3][4] 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.
[5] 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).
In Escherichia coli, Pasteurella haemolytica, and Vibrio cholerae, TolC functions as the OMP in T1SS RTX toxin export.
The RTX-activating acyltransferase catalyzes the attachment of acyl-linked fatty acids to internally located lysine residues within the RTX toxin.
[3] Pore-formation is the only known shared function in RTX cytotoxins, and pores are typically cation-selective allowing for an influx of Ca2+ in target cells.
[10] These toxins recognize protein receptors such as the β2-integrins, form pores at high concentrations, and cause cell rupture by mechanisms not well understood.
However, at low, sublytic concentrations, leukotoxin (TC# 1.C.11.1.1) causes activation of neutrophils, production of inflammatory cytokines, degranulation, generation of oxygen-derived free radicals, and morphologic changes consistent with apoptosis.
The C-terminal domain of the adenylate cyclase toxin (ACT or CyaA; TC# 1.C.11.1.4) of Bordetella pertussis forms a small cation-selective channel, disrupting the permeability barrier.
[14] The generalized transport reaction proposed for members of the RTX-toxin family is:[8] RTX toxins are produced by a variety of gram-negative bacteria.
The prototypical RTX toxin, α-haemolysin (HlyA; TC# 1.C.11.1.3), is a common virulence factor in uropathogenic E. coli (UPEC), the leading cause of urinary tract infections.
In V. cholerae infection, the CPD binds to inositol hexakisphosphate (InsP6, Phytic acid) inside eukaryotic host cells.
ACD cross-links monomeric G-actin in the host cell cytosol, preventing formation of actin microfilament, a major component of the cytoskeleton.
CyaA is a multifunctional RTX family toxin that targets myeloid phagocytes, impairing the innate immune response and promoting B. pertussis colonization.
CyaA binds the αMβ2 integrin, inserts itself into the cell membrane and opens a transient path for influx of Ca2+ ions that activate calpain.