Abstract
Staphylococcal alpha-toxin, archetype of an oligomerizing pore-forming toxin, is produced and secreted as a water-soluble 34 kD monomer. High affinity binding possibly occurs to clustered phosphocholine head groups in cholesterol/sphingomyelin-rich membrane microdomains. Toxin heptamers can rapidly assemble at such sites, and oligomerization triggers conformational changes leading to insertion of an amphipathic hairpin b-barrel sequence into the lipid bilayer, so that a protein-lined pore of approximately 1 nm diameter is formed. Many cellular reactions are triggered by the uncontrolled transmembrane flux of ions, and these can account for short- and long-range effects of the toxin. Moreover, nucleated cells can repair a limited number of membrane lesions, and transcriptional responses are then triggered that further contribute to long-term effects of the toxin. The biological relevance of the toxin is well established, and novel prophylactic and therapeutic strategies targeting this major virulence factor of S. aureus are currently being developed.
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Bhakdi, S., Walev, I., Husmann, M., Valeva, A. Staphylococcal alpha-toxin. In: Schmitt, M.J., Schaffrath, R. (eds) Microbial Protein Toxins. Topics in Current Genetics, vol 11. Springer, Berlin, Heidelberg. https://doi.org/10.1007/b100513
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DOI: https://doi.org/10.1007/b100513
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