Identification of compounds for inactivation of Shiga-like toxins (Stx) from Shiga toxin producing E. coli (STEC)

During infection toxin producing Escherichia coli releases a toxic compound called Shiga-like toxin. Shiga-like toxin is responsible for damaging the ribosome, inhibiting protein synthesis. Production of toxin can be upregulated by treatment with antibiotics commonly used to treat conditions such as chest and intestinal infections. The effect of the toxins action causes cell-death, tissue damage of the kidneys and central nervous system and is associated with poor patient outcomes. As an alternative form of therapy, we aim to improve the ability of previously identified compounds to irreversibly inactivate the toxin and prevent the subsequent toxin binding to the target. Using a range of investigative techniques, we aim to identify the ability of the compounds to prevent Shiga-like toxin inducing ribosome damage and prove the compound binds to the intended target. In collaboration with Dr David France's team at University of Glasgow Chemistry Department we will design compounds to improve the ability to bind to the target and explore whether further modifications improve absorption, distribution, metabolism, excretion, and toxicity of the compounds. Collectively these studies will contribute to the development of a specific inhibitor against Shiga-like toxins to improve to outcome of infection for patients.