title: Systemic effects of Subtilase cytotoxin produced by Escherichia coli O113:H21.
abstract: Subtilase cytotoxin (SubAB) is a member of the AB5cytotoxin family and is produced by certain 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 sublethal dose of SubAB in rats triggers a systemic response, with ascitic fluid accumulation, heart hypertrophy and damage to the liver, colon and kidney. SubAB treated rats presented microalbuminuria 20 days post inoculation. At this time we found disruption of the glomerular filtration barrier and alteration of the protein reabsorption mechanisms of the proximal tubule. In the kidney, SubAB also triggered an epithelial to mesenchymal transition (Wuyts et al., 1996). These findings indicate that apart from direct cytotoxic effects on renal tissues, SubAB causes significant damage to the other organs, with potential consequences for HUS pathogenesis.
  
  
  OBJECTIVE
  Uremic Hemolytic Syndrome is an endemic disease in Argentina, with over 400 hundred new cases each year. We have previously described renal effects of Shiga Toxin and its ability to alter renal protein handling. Bearing in mind that Subtilase Cytotoxin is an emerging pathogenic factor, that it is not routinely searched for in patients with HUS, and that to the date its systemic effects have not been fully clarified we decided to study both its systemic effects, and its renal effects to assess whether SubAB could be contributing to pathology seen in children.
authors.affiliation: Universidad de Buenos Aires, Facultad de Medicina, Instituto de Fisiología y Biofísica IFIBIO Houssay-CONICET, Argentina.
authors.forename: E Abril
authors.initials: EA
authors.lastname: Seyahian
authors.affiliation: Universidad de Buenos Aires, Facultad de Medicina, Instituto de Fisiología y Biofísica IFIBIO Houssay-CONICET, Argentina.
authors.forename: Gisela
authors.initials: G
authors.lastname: Oltra
authors.affiliation: Universidad de Buenos Aires, Facultad de Medicina, Instituto de Fisiología y Biofísica IFIBIO Houssay-CONICET, Argentina.
authors.forename: Federico
authors.initials: F
authors.lastname: Ochoa
authors.affiliation: Universidad de Buenos Aires, Facultad de Medicina, Instituto de Fisiología y Biofísica IFIBIO Houssay-CONICET, Argentina.
authors.forename: Santiago
authors.initials: S
authors.lastname: Melendi
authors.affiliation: Hospital de Agudos Juan A. Fernandez, Laboratorio Central, Argentina.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Hermes
authors.affiliation: University of Adelaide, Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, Australia.
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.affiliation: University of Adelaide, Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, Australia.
authors.forename: Adrienne W
authors.initials: AW
authors.lastname: Paton
authors.affiliation: Universidad de Buenos Aires, Facultad de Medicina, Laboratorio de Patología Experimental y Aplicada, Argentina.
authors.forename: Nestor
authors.initials: N
authors.lastname: Lago
authors.affiliation: Universidad de Buenos Aires, Facultad de Medicina, Instituto de Fisiología y Biofísica IFIBIO Houssay-CONICET, Argentina.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Castro Parodi
authors.affiliation: Universidad de Buenos Aires, Facultad de Medicina, Instituto de Fisiología y Biofísica IFIBIO Houssay-CONICET, Argentina.
authors.forename: Alicia
authors.initials: A
authors.lastname: Damiano
authors.affiliation: Universidad de Buenos Aires, Facultad de Medicina, Instituto de Fisiología y Biofísica IFIBIO Houssay-CONICET, Argentina.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ibarra
authors.affiliation: Universidad de Buenos Aires, Facultad de Medicina, Instituto de Fisiología y Biofísica IFIBIO Houssay-CONICET, Argentina; Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Fisiopatología, Buenos Aires, Argentina. Electronic address: ezotta@fmed.uba.ar.
authors.forename: Elsa
authors.initials: E
authors.lastname: Zotta
mesh_terms: D000419:Albuminuria / Q000139:chemically induced; D000818:Animals; D001201:Ascites / Q000139:chemically induced; D006332:Cardiomegaly / Q000139:chemically induced; D003106:Colon / Q000187:drug effects / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D029968:Escherichia coli Proteins / Q000378:metabolism* / Q000633:toxicity; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D017207:Rats, Sprague-Dawley; D054323:Shiga-Toxigenic Escherichia coli / Q000378:metabolism*; D013381:Subtilisins / Q000378:metabolism* / Q000633:toxicity
chemical_list: D029968:Escherichia coli Proteins; D013381:Subtilisins; C527234:subtilase cytotoxin, E coli
keywords: Kidney; Megalin; Renal protein handling; SubAB cytotoxin