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

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 cocul...

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Autores principales: Álvarez, Romina S., Gómez, Fernando D., Zotta, Elsa, Paton, Adrienne W., Paton, James C., Ibarra, Cristina, Sacerdoti, Flavia, Amaral, María M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402323/
https://www.ncbi.nlm.nih.gov/pubmed/34437406
http://dx.doi.org/10.3390/toxins13080536
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author Álvarez, Romina S.
Gómez, Fernando D.
Zotta, Elsa
Paton, Adrienne W.
Paton, James C.
Ibarra, Cristina
Sacerdoti, Flavia
Amaral, María M.
author_facet Álvarez, Romina S.
Gómez, Fernando D.
Zotta, Elsa
Paton, Adrienne W.
Paton, James C.
Ibarra, Cristina
Sacerdoti, Flavia
Amaral, María M.
author_sort Álvarez, Romina S.
collection PubMed
description 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.
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spelling pubmed-84023232021-08-29 Combined Action of Shiga Toxin Type 2 and Subtilase Cytotoxin in the Pathogenesis of Hemolytic Uremic Syndrome Álvarez, Romina S. Gómez, Fernando D. Zotta, Elsa Paton, Adrienne W. Paton, James C. Ibarra, Cristina Sacerdoti, Flavia Amaral, María M. Toxins (Basel) Article 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. MDPI 2021-07-29 /pmc/articles/PMC8402323/ /pubmed/34437406 http://dx.doi.org/10.3390/toxins13080536 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Álvarez, Romina S.
Gómez, Fernando D.
Zotta, Elsa
Paton, Adrienne W.
Paton, James C.
Ibarra, Cristina
Sacerdoti, Flavia
Amaral, María M.
Combined Action of Shiga Toxin Type 2 and Subtilase Cytotoxin in the Pathogenesis of Hemolytic Uremic Syndrome
title Combined Action of Shiga Toxin Type 2 and Subtilase Cytotoxin in the Pathogenesis of Hemolytic Uremic Syndrome
title_full Combined Action of Shiga Toxin Type 2 and Subtilase Cytotoxin in the Pathogenesis of Hemolytic Uremic Syndrome
title_fullStr Combined Action of Shiga Toxin Type 2 and Subtilase Cytotoxin in the Pathogenesis of Hemolytic Uremic Syndrome
title_full_unstemmed Combined Action of Shiga Toxin Type 2 and Subtilase Cytotoxin in the Pathogenesis of Hemolytic Uremic Syndrome
title_short Combined Action of Shiga Toxin Type 2 and Subtilase Cytotoxin in the Pathogenesis of Hemolytic Uremic Syndrome
title_sort combined action of shiga toxin type 2 and subtilase cytotoxin in the pathogenesis of hemolytic uremic syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402323/
https://www.ncbi.nlm.nih.gov/pubmed/34437406
http://dx.doi.org/10.3390/toxins13080536
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