Group a Streptococcus induces apoptosis in human epithelial cells

Pei-Jane Tsai, Yee-Shin Lin, Chih Feng Kuo, Huan Yao Lei, Jiunn Jong Wu

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Abstract

Internalization of group A streptococcus (GAS) by epithelial cells may have a role in causing invasive diseases. The purpose of this study was to examine the fate of GAS-infected epithelial cells. GAS has the ability to invade A-549 and HEp-2 cells. Both A-549 and HEp-2 cells were killed by infection with GAS. Epithelial cell death mediated by GAS was at least in part through apoptosis, as shown by changes in cellular morphology, DNA fragmentation laddering, and propidium iodide staining for hypodiploid cells. A total of 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 spontaneous apoptosis. We further examined whether streptococcal pyrogenic exotoxin B (SPE B), a cysteine protease produced by GAS, was involved in the apoptosis of epithelial cells. The speB isogenic mutants had less ability to induce cell death than wild-type strains. When A-549 cells were cocultured with 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 level of wild-type strains. In addition, apoptosis was blocked by cytochalasin D treatment, which interfered with cytoskeleton function. The caspase inhibitors Z-VAD.FMK, Ac-YVAD.CMK, and Ac-DEVD.FMK inhibited GAS-induced apoptosis. These results demonstrate for the first time that GAS induces apoptosis of epithelial cells and internalization is required for apoptosis. The caspase pathway is involved in GAS-induced apoptosis, and the expression of SPE B in the cells enhances apoptosis.

Original languageEnglish
Pages (from-to)4334-4339
Number of pages6
JournalInfection and Immunity
Volume67
Issue number9
Publication statusPublished - 1999 Sep 1

Fingerprint

Streptococcus
Epithelial Cells
Apoptosis
Cell Death
Cytochalasin D
Caspase Inhibitors
Cysteine Proteases
Propidium
DNA Fragmentation
Caspases
Infection
Cytoskeleton
Staining and Labeling
Bacteria

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Tsai, Pei-Jane ; Lin, Yee-Shin ; Kuo, Chih Feng ; Lei, Huan Yao ; Wu, Jiunn Jong. / Group a Streptococcus induces apoptosis in human epithelial cells. In: Infection and Immunity. 1999 ; Vol. 67, No. 9. pp. 4334-4339.
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Group a Streptococcus induces apoptosis in human epithelial cells. / Tsai, Pei-Jane; Lin, Yee-Shin; Kuo, Chih Feng; Lei, Huan Yao; Wu, Jiunn Jong.

In: Infection and Immunity, Vol. 67, No. 9, 01.09.1999, p. 4334-4339.

Research output: Contribution to journalArticle

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AU - Tsai, Pei-Jane

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