Abstract

Aurodox is an elfamycin-like natural product from the soil bacterium Streptomyces goldiniensis, that can block translation through inhibition of elongation factor (EF-Tu) but has also recently been shown to inhibit Type III Secretion Systems. To gain a better understanding of its mechanism of action and to assess the utility of this compound as an anti-virulence molecule we have been using a multidisciplinary approach to understand the mode of action and biosynthesis of aurodox. Investigating the mode of action of aurodox in Shiga Toxin-producing Escherichia coli (STEC) we have shown that it downregulates expression of T3SS , inhibits epithelial colonisation and does not activate the SOS response that results in Shiga toxin production. We have also shown that aurodox protects mice from Shiga-toxin mediated renal injury and colonic hyperplasia. In parallel we have identified and cloned the biosynthetic gene cluster responsible for the biosynthesis of aurodox by Streptomyces goldiniensis, predicting, characterising and dissecting its biosynthetic pathway, opening routes to engineering novel aurodox derivatives. These data suggest that aurodox may represent a useful candidate therapeutic for the treatment of STEC infections.

Biography Professor Paul A Hoskisson Paul Hoskisson is the Royal Academy of Engineering Research Chair in Engineering biology at the University of Strathclyde. Paul completed his first degree at Liverpool John Moores University in 1997 in Applied Microbiology, before a short period in the industry developing Influenza vaccines. He completed his PhD in 2001, studying gentamicin production by the bacterium Micromonospora. Post-doctoral work at the John Innes Centre (Norwich) and University of Aberdeen – working on various aspects of Streptomyces biology was followed by a move to the University of Strathclyde in 2007. The research in Paul’s laboratory is focused on evolution of antibiotic biosynthesis, evolution and domestication of antibiotic producing strains by Streptomyces, bacteriophage resistance in Streptomyces and antimicrobial resistance.

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