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

Autor:	Romina Soledad Alvarez, James C. Paton, Fernando D. Gómez, Elsa Zotta, María Marta Amaral, Adrienne W. Paton, Flavia Sacerdoti, Cristina Ibarra
Rok vydání:	2021
Předmět:	Male 0301 basic medicine Cell Survival Health Toxicology and Mutagenesis Kidney Glomerulus 030106 microbiology Subtilase cytotoxin Biology Kidney Toxicology medicine.disease_cause Shiga Toxin 2 Article Microbiology Kidney Tubules Proximal Pathogenesis 03 medical and health sciences fluids and secretions Shiga toxin-producing Escherichia coli STX2 In vivo medicine Animals Humans Subtilisins Cell damage Cells Cultured Mice Inbred BALB C Toxin Escherichia coli Proteins Endothelial Cells Epithelial Cells Shiga toxin Shiga toxin type 2 bacterial infections and mycoses medicine.disease Coculture Techniques In vitro Epithelium 030104 developmental biology medicine.anatomical_structure Hemolytic-Uremic Syndrome hemolytic uremic syndrome biology.protein Medicine bacteria co-action
Zdroj:	Toxins Volume 13 Issue 8 Toxins, Vol 13, Iss 536, p 536 (2021)
ISSN:	2072-6651
DOI:	10.3390/toxins13080536
Popis:	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.
Databáze:	OpenAIRE
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