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Toxins 2016, 8(3), 77; doi:10.3390/toxins8030077

Shiga Toxins as Multi-Functional Proteins: Induction of Host Cellular Stress Responses, Role in Pathogenesis and Therapeutic Applications

1
Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon 34141, Korea
2
Research Center for Viral Infectious Diseases and Control, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon 34141, Korea
3
Department of Neuroscience and Experimental Therapeutics, Texas A & M University Health Science Center, Bryan, TX 77807, USA
4
Department of Microbial Pathogenesis and Immunology, Texas A & M University Health Science Center, Bryan, TX 77807, USA
*
Authors to whom correspondence should be addressed.
Academic Editors: Gerald B. Koudelka and Steven A. Mauro
Received: 22 October 2015 / Revised: 25 February 2016 / Accepted: 29 February 2016 / Published: 17 March 2016
(This article belongs to the Collection Shiga Toxins)
View Full-Text   |   Download PDF [1448 KB, uploaded 17 March 2016]   |  

Abstract

Shiga toxins (Stxs) produced by Shiga toxin-producing bacteria Shigella dysenteriae serotype 1 and select serotypes of Escherichia coli are primary virulence factors in the pathogenesis of hemorrhagic colitis progressing to potentially fatal systemic complications, such as hemolytic uremic syndrome and central nervous system abnormalities. Current therapeutic options to treat patients infected with toxin-producing bacteria are limited. The structures of Stxs, toxin-receptor binding, intracellular transport and the mode of action of the toxins have been well defined. However, in the last decade, numerous studies have demonstrated that in addition to being potent protein synthesis inhibitors, Stxs are also multifunctional proteins capable of activating multiple cell stress signaling pathways, which may result in apoptosis, autophagy or activation of the innate immune response. Here, we briefly present the current understanding of Stx-activated signaling pathways and provide a concise review of therapeutic applications to target tumors by engineering the toxins. View Full-Text
Keywords: Shiga toxins; Shiga toxin type 1 and 2; Shiga toxin-producing Escherichia coli; hemolytic uremic syndrome; signaling pathways; cancer therapeutics Shiga toxins; Shiga toxin type 1 and 2; Shiga toxin-producing Escherichia coli; hemolytic uremic syndrome; signaling pathways; cancer therapeutics
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Lee, M.-S.; Koo, S.; Jeong, D.G.; Tesh, V.L. Shiga Toxins as Multi-Functional Proteins: Induction of Host Cellular Stress Responses, Role in Pathogenesis and Therapeutic Applications. Toxins 2016, 8, 77.

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