Sublytic Concentrations of Staphylococcus Aureus α-Toxin Trigger Na+/K+ Atpase Mediated Cell Shrinkage

Abstract

Cell lysis can occur through the pathologic action of various membrane-targeting toxins, of which the pore-forming toxin Staphylococcus aureus α-toxin is a prominent example. Paradoxically, S. aureus α-toxin, which forms monovalent cation permeable channels in the host cell plasma membrane, has been observed to cause significant volume shrinkage in many cell types. In HeLa cells we note a ≈45% decrease in cell volume 30-60 mins post α-toxin treatment in both interphase and mitotic cells. We show that inhibition of the Na+/K+ ATPase pump with ouabain not only prevents the cell shrinkage, but leads to cell volume expansion after exposure to α-toxin. This suggests α-toxin mediated volume decrease occurs through the upregulation of Na+/K+ ATPase activity because the 3:2 export:import ratio of Na+:K+ leads to the loss of one osmolyte per cycle. We therefore conclude that α-toxin induced cell shrinkage is an active cellular process driven by the Na+/K+ ATPase and elucidate sub-lytic mechanisms of pore-forming toxin assault.