Elimination of a bacterial pore-forming toxin by sequential endocytosis and exocytosis

Abstract 

Staphylococcus aureus α-toxin is the archetype of bacterial pore forming toxins and a key virulence factor secreted by the majority of clinical isolates of S. aureus. Toxin monomers bind to target cells and oligomerize to form small β-barrel pores in the plasma membrane. Many nucleated cells are able to repair a limited number of lesions by unknown, calcium-independent mechanisms. Here we show that cells can internalize α-toxin, that uptake is essential for cellular survival, and that pore-complexes are not proteolytically degraded, but returned to the extracellular milieu in the context of exosome-like structures, which we term toxosomes.

Abbreviation: 1mer, α-toxin monomer, 7mer, α-toxin heptamer, CSPL, cell surface protein labeling, IP, immunoprecipitation, MVB, multivesicular bodies, PFT, pore forming toxins, SLO, streptolysin O, Tbl, Trypan blue

Keywords: α-Toxin, Bacterial pore forming toxin, Endocytosis, Exosome, Innate defence mechanism, Staphylococcus aureus