title: Recent progress of Shiga toxin neutralizer for treatment of infections by Shiga toxin-producing Escherichia coli.
abstract: Infection with Shiga toxin (Stx)-producing Escherichia coli (STEC), including O157:H7, causes bloody diarrhea and hemorrhagic colitis in humans, occasionally resulting in fatal systemic complications, such as neurological damage and hemolytic-uremic syndrome. Because Stx is a major virulence factor of the infectious disease, a series of Shiga toxin neutralizers with various structural characteristics has been developed as promising therapeutic agents. Most of these agents function to bind to the toxin directly and inhibit the binding to its receptor present on the target cells. Other neutralizers do not inhibit receptor binding but induce aberrant intracellular transport of the toxin, resulting in effective detoxification. Such a novel type of Stx neutralizer provides a new therapeutic strategy against STEC infections. Here, recent progress of the development of Stx neutralizers is reviewed.
authors.affiliation: Faculty of Life and Medical Sciences, Department of Molecular Life Sciences, Doshisha University, Tatara, Kyotanabe, Kyoto, Japan. knishika@mail.doshisha.ac.jp
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000627:therapeutic use; D001665:Binding Sites / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D015195:Drug Design; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004927:Escherichia coli Infections / Q000188:drug therapy*; D019453:Escherichia coli O157 / Q000378:metabolism; D005915:Globosides / Q000378:metabolism; D006463:Hemolytic-Uremic Syndrome / Q000382:microbiology; D006801:Humans; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis; D011108:Polymers / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D000683:Serum Amyloid P-Component / Q000378:metabolism / Q000627:therapeutic use; D022622:Shiga Toxin 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D022641:Shiga Toxin 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012821:Silanes / Q000138:chemical synthesis / Q000627:therapeutic use; D014281:Trihexosylceramides / Q000008:administration & dosage*; D014312:Trisaccharides / Q000138:chemical synthesis / Q000627:therapeutic use; D037521:Virulence Factors / Q000378:metabolism
chemical_list: C546398:Ac-PPP-tet; D000900:Anti-Bacterial Agents; D005915:Globosides; D010455:Peptides; D011108:Polymers; D000683:Serum Amyloid P-Component; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; D012821:Silanes; D014281:Trihexosylceramides; D014312:Trisaccharides; D037521:Virulence Factors; C024032:globotetraosylceramide; C018549:globotriaosylceramide