Staphylococcal alpha-toxin kills human keratinocytes by permeabilizing the plasma membrane for monovalent ions

I. Walev, E. Martin, D. Jonas, M. Mohamadzadeh, W. Muller-Klieser, L. Kunz, S. Bhakdi

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

Incubation of human keratinocytes with nanomolar concentrations of Staphylococcus aureus alpha-toxin leads to irreversible depletion of cellular ATP. The toxin forms hexamers in the target cell membranes, and rapid transmembrane flux of K+, Na+, and 86Rb+ is observed. Unexpectedly, pores formed in keratinocytes through application of low but lethal doses of alpha-toxin appeared to be considerably smaller than those formed in erythrocyte membranes. They permitted neither rapid influx of Ca2+ or propidium iodide, nor efflux of carboxyfluorescein. Larger pores allowing flux of all three markers did form when the toxin was applied at high concentrations. Flux of monovalent ions and reduction in cellular ATP levels evoked by low toxin doses correlated temporally with a fall in oxygen consumption, which was interpreted to reflect breakdown of mitochondrial respiration. The lethal event could not be thwarted by manipulating the extracellular K+ or Ca2+ concentrations. Realization that alpha-toxin may form very small pores in nucleated cells is important for future research on cellular toxin effects and membrane repair processes.

Original languageEnglish (US)
Pages (from-to)4972-4979
Number of pages8
JournalInfection and immunity
Volume61
Issue number12
StatePublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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