Staphylococcus aureus α-toxin-induced cell death: predominant necrosis despite apoptotic caspase activation

Abstract

Recent data suggest that a-toxin, the major hemolysin of Staphylococcus aureus, induces cell death via the classical apoptotic pathway. Here we demonstrate, however, that although zVAD-fmk or overexpression of Bcl-2 completely abrogated caspase activation and internucleosomal DNA fragmentation, they did not significantly affect a-toxin-induced death of Jurkat T or MCF-7 breast carcinoma cells. Caspase inhibition had also no effect on a-toxin-induced lactate dehydrogenase release and ATP depletion. Furthermore, whereas early assessment of apoptosis induction by CD95 resulted solely in the generation of cells positive for active caspases that were, however, not yet permeable for propidium iodide, a substantial proportion of a-toxin-treated cells were positive for both active caspases and PI. Finally, electron microscopy demonstrated that even in the presence of active caspases, a-toxin-treated cells displayed a necrotic morphology characterized by cell swelling and cytoplasmic vacuolation. Together, our data suggest that a-toxin-induced cell death proceeds even in the presence of activated caspases, at least partially, in a caspase-independent, necrotic-like manner.

Cytolethal Distending Toxin Induces Caspase-Dependent and -Independent Cell Death in MOLT-4 Cells

“…Staphylococcus aureus alpha-toxin, the major hemolysin, induces massive cell necrosis by forming pores in lipid bilayers at high doses (Ͼ6 g/ml). At low doses, this toxin can induce DNA fragmentation and caspase activation, the typical classical apoptosis pathway, and also caspaseindependent cell death (11). Streptococcus pneumoniae induces a rapid caspase-independent cell death in cultured bone mar- row-derived dendritic cells (6).…”

The tail-anchoring domain of Bfl1 and HCCS1 targets mitochondrial membrane permeability to induce apoptosis

“…To analyze DNA fragmentation by agarose gel electrophoresis, cellular DNA was prepared as described (Essmann et al, 2003). 24 hours after transfection, cells in 35 mm wells were lysed in 0.2 ml lysis buffer (20 mM Tris-HCl, 0.5 mM EDTA, pH 8.0) containing 0.25% NP-40 and 50 g RNase A at 37°C for 30 minutes.…”

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

“…Membrane-associated a-toxin monomers assemble into heptameric ring-like structures, which can insert an amphipathic amino acid sequence to generate a b-barrel traversing the lipid bilayer [15,16]. In erythrocytes, a-toxin induces colloidosmotic lysis [17], whereas attack on nucleated target cells causes necrosis [18] or apoptosis [19]. Cell death is, however, not an inevitable consequence of pore-formation.…”