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

Edited by Aleksander Benjak

Received 14 November 2008; received in revised form 4 December 2008; accepted 9 December 2008. published online 19 December 2008.

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

a Institute of Medical Microbiology and Hygiene, Johannes Gutenberg-University Mainz, Hochhaus am Augustusplatz, 55131 Mainz, Germany

b Paul Ehrlich-Institute, Department of Immunology, Morphology Section, 63225 Langen, Germany

c Institute of Immunology, Johannes Gutenberg-University Mainz, 55131 Mainz, Germany

d Chemical Research Laboratory, Chemical Biology Sub-Department, University of Oxford, Oxford OX1 3TA, England, UK

Corresponding author. Fax: +49 06131 3932359.

PII: S0014-5793(08)01002-8

doi:10.1016/j.febslet.2008.12.028

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