Systemic effects of Subtilase cytotoxin produced by Escherichia coli O113:H21.

SEYAHIAN ABRIL; OLTRA GISELA; OCHOA FEDERICO; MELENDI SANTIAGO; HERMES RICARDO; PATON JAMES; PATON ADRIENNE; LAGO NESTOR; CASTRO PARODI MAURICIO; DAMIANO ALICIA; IBARRA CRISTINA; ZOTTA ELSA

TOXICON

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2017 vol. 127 p. 49 - 55

0041-0101

Subtilase cytotoxin (SubAB) is a member of the AB5 cytotoxin family and is produced bycertain strains of Shiga toxigenic Escherichia coli. The toxin is known to be lethal to mice,but the pathological mechanisms that contribute to Uremic Hemolytic Syndrome (HUS)are poorly understood. In this study we show that intraperitoneal injection of a sublethaldose of SubAB in rats triggers a systemic response, with ascitic fluid accumulation, hearthypertrophy and damage to the liver, colon and kidney. SubAB treated rats presentedmicroalbuminuria 20 days post inoculation. At this time we found disruption of theglomerular filtration barrier and alteration of the protein reabsorption mechanisms of the proximal tubule. In the kidney, SubAB also triggered an epithelial to mesenchymaltransition (1). These findings indicate that apart from direct cytotoxic effects on renaltissues, SubAB causes significant damage to the other organs, with potentialconsequences for HUS pathogenesis.Importance: Uremic Hemolytic Syndrome is an endemic disease in Argentina, with over400 hundred new cases each year. We have previously described renal effects of ShigaToxin and its ability to alter renal protein handling. Bearing in mind that SubtilaseCytotoxin is an emerging pathogenic factor, that it is not routinely searched for in patientswith HUS, and that to the date its systemic effects have not been fully clarified we decidedto study both its systemic effects, and its renal effects to assess whether SubAB could becontributing to pathology seen in children.