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

Staphylococcus aureus alpha-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 beta-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 alpha-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. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.