Combined Action of Shiga Toxin Type 2 and Subtilase Cyto- toxin in the Pathogenesis of Hemolytic Uremic Syndrome

ALVAREZ ROMINA; GOMEZ FERNANDO D; ZOTTA ELSA ; PATON ADRIENNE; PATON JAMES; IBARRA CRISTINA; SACERDOTI FLAVIA; AMARAL MARÍA MARTA

Toxins (Basel)

MDPI

Año: 2021 vol. 13

2072-6651

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 ofthis work was to study the co-action of Stx2 and SubAB. Stx2 + SubAB was assayed in vitro onmonocultures and cocultures of human glomerular endothelial cells (HGEC) with a human proxi-mal tubular epithelial cell line (HK-2) and in vivo in mice after weaning. The effects in vitro of bothtoxins, co-incubated and individually, were similar, showing that Stx2 and SubAB contribute simi-larly to renal cell damage. However, in vivo, co-injection of toxins lethal doses reduced the survivaltime of mice by 24 h and mice also suffered a strong decrease in the body weight associated with alowered food intake. Co-injected mice also exhibited more severe histological renal alterations anda 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 in-crease of free hemoglobin. This work shows, for the first time, the in vivo effects of Stx2 and SubABacting together and provides valuable information about their contribution to the damage causedin STEC infections.