Molecular mechanisms of Shiga toxin action in the mammal central nervous system

Obata, Fumiko

Abstract

Shiga toxin producing Escherichia coli (STEC) infection causes diarrhea, bloody diarrhea and in severe cases, patients develop Hemolytic Uremic Syndrome (HUS) and central nervous system (CNS) impairment. STEC induced neuronal disabilities includes a broad spectrum of symptoms as cortical blindness, poor fine-motor coordination, seizures and changes in consciousness including coma. Importantly, CNS manifestations often associate with mortality or severe sequelae. STEC produce Shiga toxins 1 and 2 (Stx1 and Stx2); among them, Stx2 is more potent as a cause of severe HUS and CNS impairment. However, precise mechanisms of Shiga toxin induced CNS impairment are not yet clear. I propose to reveal the mechanisms of Shiga toxin action in the CNS by using in vitro neuron-astrocytic cell culture and in vivo with the Stx2 induced hindlimb paralysis murine model.