Group A streptococcus induces apoptosis in human epithelial cells

Internalization of group A streptococcus (GAS) by epithelial cells may have a role in causing invasive diseases. The purpose of this study was to exam ine the fate of GAS-infected epithelial cells. GAS has the ability to invad e A-549 and HEp-2 cells. Both A-549 and HEp-2 cells were killed by infectio n with GAS. Epithelial cell death mediated by GAS was at least in part thro ugh apoptosis, as shown by changes in cellular morphology, DNA fragmentatio n laddering, and propidium iodide staining for hypodiploid cells. A total o f 20% of A-549 cells and 11 to 13% of HEp-2 cells underwent apoptosis after 20 h of GAS infection, whereas only 1 to 2% of these cells exhibited spont aneous apoptosis, We further examined whether streptococcal pyrogenic exoto xin B (SPE B), a cysteine protease produced by GAS, was involved in the apo ptosis of epithelial cells, The speB isogenic mutants had less ability to i nduce cell death than wild-type strains, When A-549 cells were cocultured w ith the mutant and SPE B for 2 h, the percentage of apoptotic cells did not increase although the number of intracellular bacteria increased to the le vel of wild-type strains. In addition, apoptosis was blocked by cytochalasi n D treatment, which interfered with cytoskeleton function. The caspase inh ibitors Z-VAD.FMK, Ac-YVAD.CMK, and Ac-DEVD.FMK inhibited GAS-induced apopt osis, These results demonstrate for the first time that GAS induces apoptos is of epithelial cells and internalization is required for apoptosis. The c aspase pathway is involved in GAS-induced apoptosis, and the expression of SPE B in the cells enhances apoptosis.