title: Elimination of a bacterial pore-forming toxin by sequential endocytosis and exocytosis.
abstract: 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.
authors.affiliation: Institute of Medical Microbiology and Hygiene, Johannes Gutenberg-University Mainz, Hochhaus am Augustusplatz, 55131 Mainz, Germany. MattHusmann@web.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Husmann
authors.forename: Erik
authors.initials: E
authors.lastname: Beckmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Boller
authors.forename: Nicole
authors.initials: N
authors.lastname: Kloft
authors.forename: Stefan
authors.initials: S
authors.lastname: Tenzer
authors.forename: Wiesia
authors.initials: W
authors.lastname: Bobkiewicz
authors.forename: Claudia
authors.initials: C
authors.lastname: Neukirch
authors.forename: Hagan
authors.initials: H
authors.lastname: Bayley
authors.forename: Sucharit
authors.initials: S
authors.lastname: Bhakdi
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D009154:Mutation
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D018942:Macrolides; C021091:staphylococcal alpha-toxin; C057620:bafilomycin A