1.C.70 The Streptococcal Pore-forming CAMP Factor (CAMP-F) Family
Streptococcus pyogenes, S. agalastiae, S. uberis and S. canis contain related pore-forming toxins called CAMP factors. They are about 255 aas long and have a single N-terminal TMS. The S. pyogenes and S. agalactiae homologues are 60% identical. CAMP factors are hemolytic and form discrete transmembrane oligomeric pores with diameters of about 1.6 nm. Electron microscopy reveals circular membrane lesions of heterogeneous sizes, up to 12-15 nm in diameter (Lang and Palmer, 2003). The toxin allows the passive diffusion of small molecules across the membrane. Toxic activity depends on the presence of sphingomyelin (50%, 20% and 19% in sheep, human and rabbit red blood cells, respectively).
The structure of this toxin has been determined, revealing a structural fold composed of 5 + 3-helix bundles. The N-terminal 5-helix bundle is responsible for membrane permeabilization, whereas the C-terminal 3-helix bundle is likely responsible for host receptor binding. The C-terminal domain inhibited the activity of both full-length toxin and its N-terminal domain. The linker region is highly conserved and has a conserved DLXXXDXAT sequence motif. This linker region interacted with both terminal CAMP factor domains, and mutagenesis disclosed that the conserved sequence motif is required for CAMP factor's co-hemolytic activity (Jin et al. 2018).