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Disarm and disengage: Understanding Aurodox - a Type III Secretion System inhibitor from Streptomyces
Aurodox is an elfamycin-like natural product from the soil bacterium Streptomyces goldiniensis, that can block translation through inhibition of elongation factor 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. Our data suggest that aurodox may represent a useful candidate therapeutic for the treatment of STEC infections.
Date:
29 November 2024, 14:00
Venue:
Medical Sciences Teaching Centre, off South Parks Road OX1 3PL
Venue Details:
Lecture Theatre
Speaker:
Prof Paul Hoskisson (University of Strathclyde)
Organising department:
Sir William Dunn School of Pathology
Organiser:
Melissa Wright (Sir William Dunn School of Pathology)
Organiser contact email address:
melissa.wright@path.ox.ac.uk
Host:
Dr Georgia Isom (Sir William Dunn School of Pathology)
Part of:
Dunn School of Pathology Departmental Seminars
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Melissa Wright
