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Characterisation of the mode of action of Aurodox, a type III secretion system inhibitor from streptomyces goldiniensis

McHugh, Rebecca E and O'Boyle, Nicky and Connolly, James P R and Hoskisson, Paul A and Roe, Andrew J (2018) Characterisation of the mode of action of Aurodox, a type III secretion system inhibitor from streptomyces goldiniensis. Infection and Immunity. ISSN 0019-9567

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Abstract

Recent work has demonstrated that the polyketide natural product Aurodox, from Streptomyces goldiniensis is able to block the pathogenesis of the murine pathogen Citrobacter rodentium In this work we aimed to aimed gain a better understanding of the mechanism of action of the compound. We show that Aurodox downregulates the expression of the Type Three Secretion Systems of enteropathogenic and enterohaemorhagic Escherichia coli Furthermore, we have used transcriptomic analysis to show that Aurodox inhibits the expression at the transcriptional level by repressing the master regulator, ler Our data support a model in which Aurodox acts upstream of ler and not directly on the secretion system itself. Finally, we have shown that Aurodox, unlike some traditional antibiotics, does not induce expression of RecA, which is essential for the production of Shiga toxin. We propose that these properties nominate Aurodox as a promising anti-virulence therapy for the treatment of these infections.