Physiopathology Research Group

Infection with Shiga toxin producing Escherichia coli (STEC) serotypes causing hemorrhagic colitis is a serious public health problem in Argentina. In some cases colitis lead to a complication known as hemolitic uremic syndrome (HUS), characterized by hemolytic anemia, thrombocytopenia, renal failure and brain damage.

The main purpose of our laboratory is to investigate the physiopathological mechanisms associated with HUS in order to develop new strategies to reduce the incidence of STEC in human and cattle.

Research objetives:

To study the cellular and molecular events involved in the cytotoxic action of Shiga toxin type 2 (Stx2).
To characterize the cytotoxic action of Stx2 in an experimental model of HUS in rats. To analyze inhibitors of Gb3 synthesis as blocking agents of toxin action.
To study the Stx2 action in human placenta and in pregnant rats in order to clarify if STEC infections during pregnancy could be one of the causes not yet determined of fetal morbimortality in human pregnancy.
To investigate the cytotoxic action of subtilasa toxin that has recently identified in several STEC strain in order to know its contribution in the development of HUS.

Director:
Cristina Ibarra, PhD

Staff:
Claudia Silberstein, PhD
Elsa Zotta, MD, PhD
Marcela Belardo, PhD student
Juliana Burdet, PhD student
Elizabeth Gerhardt, PhD student
Federico Ochoa, MD, PhD student
Soledad Lucero, undergraduate student
Gisela Oltra, undergraduate student

Colaborations:

In Argentina:
Angel Cataldi, PhD, Instituto de Biotecnología, INTA-Castelar.
Ana Franchi, PhD, CEFYBO-CONICET
Basilio Kotsias, PhD, Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, UBA.
Elsa Mercado, MSc, Instituto de Patobiología, INTA-Castelar.
Marina Palermo, PhD, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina.
Horacio Repetto, MD, PhD, Depto Pediatría, Hospital Nacional “Prof. A. Posadas”.
Marta Rivas, MSc Servicio de Fisiopatogenia, Instituto Nacional de Enfermedades Infecciosas. ANLIS "Dr Carlos G. Malbrán".
Mariano Fernandez Miyakawa, PhD. Instituto de Patobiología, Centro Nacional de Investigaciones Agropecuárias, Instituto Nacional de Tecnologia Agropecuária (INTA). Castelar, Buenos Aires.

Abroad:
José Luis Perez Quiñoy, PhD, Instituto Finlay, La Habana, Cuba.
Pierre Ripoche, PhD, Institut National de la Santé et de la Recherche Medicale UMR_S 665, Université Paris-Diderot, France.
James Paton, PhD. School of Molecular and Biomedical Science, University of Adelaida, Australia.
Carlos Guzmán, PhD, Helmholtz Centre for Infection Research, Braunschweig, Alemania.

Contact:
Dr. Cristina Ibarra
Paraguay 2155, 7^mo piso
Buenos Aires - Argentina
TE: 5950-9500 interno 2141
e-mail: ibarra@fmed.uba.ar

Recent Publications (last 5 years)

Assef Y, Cavarra S, Damiano AE, Ibarra C, Kotsias B: Ionic currents in multidrug resistant K562 human leukemic cells. Leuk Res 2005; 29: 1039-47.
Pistone Creydt V, Nuñez P, Zotta E, Ibarra C: Efecto citotóxico de la toxina Shiga tipo 2 y su subunidad B en células epiteliales tubulares renales humanas en cultivo. Medicina (B Aires) 2005; 65: 147-150.
Pistone Creydt V, Venzano A, Vilte D, Mercado E, Ibarra C: Escherichia coli enterohemorrágica aislada de terneros con diarrea sanguinolenta produce efecto citotóxico en colon humano. Rev Arg Microbiol 2005; 37: 117-121.
Fernández Miyakawa M, Pistone Creydt V, Uzal FA, McClane BA, Ibarra C. Clostridium perfringens enterotoxin damages human intestine in vitro. Inf Immun 2005; 73: 8407-8410.
Pistone Creydt V, Silberstein C, Zotta E, Ibarra C: Cytotoxic effect of Shiga toxin-2 holotoxin and its B subunit on human renal tubular epithelial cells. Microbe Infec 2006; 8: 410-419.
del Monaco S, Assef Y, Damiano A, Zotta E, Ibarra C, Kotsias BA: Characterization of the epithelial sodium channel in human preeclampsia syncytiotrophoblast. Medicina (B Aires) 2006; 66: 31-35.
Damiano E, Zotta E, Ibarra C: Functional and molecular expression of AQP9 channel and UT-A transporter in normal and preeclamptic human placenta. Placenta 2006; 27: 1073-1081.
Creydt VP, Nunez P, Boccoli J, Silberstein C, Zotta E, Goldstein J, Ibarra C: Role of the Shiga toxin in the hemolytic uremic syndrome. Medicina (B Aires) 2006; 66 Suppl 3:11-15.
Fernández Miyakawa ME, Dorr R, Fernández LE, Uzal FA, Ibarra C: Simple multichannel system for the measurement of the net water flux across biological tissues. Comput Methods Program Biomed 2007; 85: 95-100.
Goldstein J, Loidl CF, Pistone Creydt V, Boccoli J, Ibarra C: Intracerebroventricular administration of Shiga toxin type 2 induces striatal neuronal death and glial alterations: an ultrastructural study. Brain Res 2007; 1161:106-115. Figura 2 K del trabajo fue elegida para la tapa de la revista.
Cavarra MS, del Mónaco S, Assef Y, Ibarra C, Kotsias BA: HERG1 currents in native K562 leukemic cells. J Membr Biol 2007; 219: 49-61.
Zotta E, Lago Nestor, Ochoa F, Repetto H, Ibarra C: Development of an experimental Hemolytic Uremic Syndrome in rats. Pediatr Nephrol 2008; 23: 559-567.
Silberstein C, Pistone Creydt V, Gerhardt E, Núñez P, Ibarra C: Inhibition of water absorption in human proximal tubular epithelial cells in response to Shiga toxin-2. Pediatr Nephrol 2008; 23: 1981-1990.
Boccoli J, Loidl F, Lopez-Costa J-J, Pistone Creydt V, Ibarra C, Goldstein J: Intracerebroventricular administration of Shiga toxin type 2 altered the expression levels of neuronal nitric oxide synthase and glial fibrillary acidic protein in rat brains. Brain Res 2008; 1230: 320-333.
Cataldi A, Yevsa T, Vilte D, Schulze K, Castro-Parodi M, Larzábal M, Ibarra C, Mercado E, Guzmán CA. Efficient immune responses against Intimin and EspB of enterohaemorragic Escherichia coli after intranasal vaccination using the TLR2/6 agonist MALP-2 as adjuvant. Vaccine 2008; 26: 5662-5667.
Ibarra C, Goldstein J, Silberstein C, Zotta E, Belardo M, Repetto HA: Síndrome Urémico Hemolítico inducido por Escherichia coli enterohemorrágica. Arch Argent Pediatr 2008; 106: 435-442.
Zotta E, Ochoa F, Tironi Farinati C, Damiano A, Silberstein C, Levy Yeyati N, Ibarra C: UT-A expression in pars recta from a rat model of chronic renal failure. J Nephrol 2008; 21: 948-959.
Silberstein C, Copeland DP, Chiang W-L, Repetto HA, Ibarra C: A glucosylceramide synthase inhibitor prevents the cytotoxic effects of Shiga toxin-2 on human renal tubular epithelial cells. J Epith Biol Pharmacol. 2008; 1: 71-75.
Burdet J, Zotta E, Franchi AM, Ibarra C: Intraperitoneal administration of Shiga toxin type 2 in rats in the late stage of pregnancy produces premature delivery of dead fetuses. Placenta 2009; 30: 491-496.