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Combined Action of Shiga Toxin Type 2 and Subtilase Cytotoxin in the Pathogenesis of Hemolytic Uremic Syndrome.

Abstract
Shiga toxin-producing E. coli (STEC) produces Stx1 and/or Stx2, and Subtilase cytotoxin (SubAB). Since these toxins may be present simultaneously during STEC infections, the purpose of this work was to study the co-action of Stx2 and SubAB. Stx2 + SubAB was assayed in vitro on monocultures and cocultures of human glomerular endothelial cells (HGEC) with a human proximal tubular epithelial cell line (HK-2) and in vivo in mice after weaning. The effects in vitro of both toxins, co-incubated and individually, were similar, showing that Stx2 and SubAB contribute similarly to renal cell damage. However, in vivo, co-injection of toxins lethal doses reduced the survival time of mice by 24 h and mice also suffered a strong decrease in the body weight associated with a lowered food intake. Co-injected mice also exhibited more severe histological renal alterations and a worsening in renal function that was not as evident in mice treated with each toxin separately. Furthermore, co-treatment induced numerous erythrocyte morphological alterations and an increase of free hemoglobin. This work shows, for the first time, the in vivo effects of Stx2 and SubAB acting together and provides valuable information about their contribution to the damage caused in STEC infections.
AuthorsRomina S Álvarez, Fernando D Gómez, Elsa Zotta, Adrienne W Paton, James C Paton, Cristina Ibarra, Flavia Sacerdoti, María M Amaral
JournalToxins (Toxins (Basel)) Vol. 13 Issue 8 (07 29 2021) ISSN: 2072-6651 [Electronic] Switzerland
PMID34437406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Escherichia coli Proteins
  • Shiga Toxin 2
  • Subtilisins
  • subtilase cytotoxin, E coli
Topics
  • Animals
  • Cell Survival (drug effects)
  • Cells, Cultured
  • Coculture Techniques
  • Endothelial Cells (drug effects)
  • Epithelial Cells (drug effects)
  • Escherichia coli Proteins (toxicity)
  • Hemolytic-Uremic Syndrome (etiology, pathology)
  • Humans
  • Kidney (drug effects, pathology)
  • Kidney Glomerulus (cytology)
  • Kidney Tubules, Proximal (cytology)
  • Male
  • Mice, Inbred BALB C
  • Shiga Toxin 2 (toxicity)
  • Subtilisins (toxicity)
  • Mice

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