Induction of apoptosis by Shiga toxins

Abstract

Shiga toxins comprise a family of structurally and functionally related protein toxins expressed by Shigella dysenteriae serotype 1 and multiple serotypes of Escherichia coli. While the capacity of Shiga toxins to inhibit protein synthesis by catalytic inactivation of eukaryotic ribosomes has been well described, it is also apparent that Shiga toxins trigger apoptosis in many cell types. This review presents evidence that Shiga toxins induce apoptosis of epithelial, endothelial, leukocytic, lymphoid and neuronal cells. Apoptotic signaling pathways activated by the toxins are reviewed with an emphasis on signaling mechanisms that are shared among different cell types. Data suggesting that Shiga toxins induce apoptosis through the endoplasmic reticulum stress response and clinical evidence demonstrating apoptosis in humans infected with Shiga toxin-producing bacteria are briefly discussed. The potential for use of Shiga toxins to induce apoptosis in cancer cells is briefly reviewed.

Keywords:

• apoptosis
• caspase 8 activation
• hemolytic uremic syndrome
• microbial pathogenesis
• Shiga toxin
• Shiga toxin-producing Escherichia coli
• Shigella dysenteriae serotype 1

Acknowledgement

The editorial assistance of Sean Cleghorn is gratefully acknowledged.

Financial & competing interests disclosure

Work in the author‘s laboratory was supported by US Public Health Services grant RO1 AI34530–12 from the National Institute of Allergy and Infectious Diseases (MD, USA). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from that disclosed.

No writing assistance was utilized in the production of the manuscript.

Additional information

Funding

Work in the author‘s laboratory was supported by US Public Health Services grant RO1 AI34530–12 from the National Institute of Allergy and Infectious Diseases (MD, USA). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from that disclosed. No writing assistance was utilized in the production of the manuscript.