Abstract
Shiga toxin (Stx) producing Escherichia coli (STEC) is responsible for causing hemolytic uremic syndrome (HUS), a life-threatening thrombotic microangiopathy characterized by thrombocytopenia, hemolytic anemia, and acute renal failure after bacterially induced hemorrhagic diarrhea. Until now, there has been neither an effective treatment nor method of prevention for the deleterious effects caused by Stx intoxication. Antibodies are well recognized as affinity components of therapeutic drugs; thus, a previously obtained recombinant human FabC11:Stx2 fragment was used to neutralize Stx2 in vitro in a Vero cell viability assay. Herein, we demonstrated that this fragment neutralized, in a dose-dependent manner, the cytotoxic effects of Stx2 on human glomerular endothelial cells, on human proximal tubular epithelial cells, and prevented the morphological alterations induced by Stx2. FabC11:Stx2 protected mice from a lethal dose of Stx2 by toxin-antibody pre-incubation. Altogether, our results show the ability of a new encouraging molecule to prevent Stx-intoxication symptoms during STEC infection.
Highlights
Shiga toxin type 2 (Stx2) is a ribotoxin produced by several strains of Shiga toxin-producingEscherichia coli (STEC), an etiologic agent of bloody diarrhea
Stx2 is part of a related bacterial toxin protein family that are similar in structure and mechanism of action, comprised of Stx from Shigella dysenteriae and Stx1 from Shiga toxin-producingEscherichia coli (STEC)
Stx2-producing strains are more virulent than Stx1-producing ones and are frequently associated with hemolytic uremic syndrome (HUS), a thrombotic microangiopathy characterized by thrombocytopenia, hemolytic anemia, and acute renal failure [5]
Summary
Shiga toxin type 2 (Stx2) is a ribotoxin produced by several strains of Shiga toxin-producingEscherichia coli (STEC), an etiologic agent of bloody diarrhea. Stx consists of seven different variants (Stx2a–Stx2g), which have high homology (93–100%), except for Stx2f (69% identity) [1]. Toxins 2018, 10, 508 are encoded by a bacteriophage genome, which can be transferred between related bacteria, resulting in a diverse array of bacterial strains secreting one or more toxin subtypes [2]. Stx is part of a related bacterial toxin protein family that are similar in structure and mechanism of action, comprised of Stx from Shigella dysenteriae and Stx from STEC. Stxs belong to the AB5 toxin protein class, consisting of an enzymatically active A subunit (~32 kDa), and a homo-pentameric B subunit (7.7 kDa per monomer) which binds to the host receptor globotriaosylceramide (Gb3 ) [3].
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