title: Shiga Toxins as Multi-Functional Proteins: Induction of Host Cellular Stress Responses, Role in Pathogenesis and Therapeutic Applications.
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.
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon 34141, Korea. msl031000@kribb.re.kr.|Research Center for Viral Infectious Diseases and Control, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon 34141, Korea. msl031000@kribb.re.kr.
authors.forename: Moo-Seung
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A &amp; M University Health Science Center, Bryan, TX 77807, USA. swkoo@tamu.edu.
authors.forename: Sunwoo
authors.initials: S
authors.lastname: Koo
authors.affiliation: Research Center for Viral Infectious Diseases and Control, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon 34141, Korea. dgjeong@kribb.re.kr.
authors.forename: Dae Gwin
authors.initials: DG
authors.lastname: Jeong
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A &amp; M University Health Science Center, Bryan, TX 77807, USA. tesh@medicine.tamhsc.edu.
authors.forename: Vernon L
authors.initials: VL
authors.lastname: Tesh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D011487:Protein Conformation; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D022603:Shiga Toxins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological
chemical_list: D000970:Antineoplastic Agents; D011500:Protein Synthesis Inhibitors; D022603:Shiga Toxins
keywords: Shiga toxin type 1 and 2; Shiga toxin-producing Escherichia coli; Shiga toxins; cancer therapeutics; hemolytic uremic syndrome; signaling pathways