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

Rebecca E McHugh, Nicky O'Boyle, James P R Connolly, Paul A Hoskisson, Andrew J Roe

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19 Citations (Scopus)
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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 gain a better understanding of the mechanism of action of the compound. We show that Aurodox down-regulates the expression of the type III secretion systems of enteropathogenic and enterohemorrhagic 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 antivirulence therapy for the treatment of these infections.

Original languageEnglish
Article numbere00595-18
Number of pages12
JournalInfection and Immunity
Issue number2
Early online date24 Jan 2019
Publication statusPublished - 28 Feb 2019


  • streptomyces goldiniensis
  • aurodox
  • citrobacter rodentium


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