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

Research output: Contribution to journalArticle

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 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.

LanguageEnglish
Article numbere00595-18
Number of pages12
JournalInfection and Immunity
Volume87
Issue number2
Early online date24 Jan 2019
DOIs
Publication statusPublished - 28 Feb 2019

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Aurodox
Streptomyces
Citrobacter rodentium
Shiga Toxin
Enterohemorrhagic Escherichia coli
Polyketides
Enteropathogenic Escherichia coli
Biological Products
Type III Secretion Systems
Down-Regulation
Anti-Bacterial Agents

Keywords

  • streptomyces goldiniensis
  • aurodox
  • citrobacter rodentium

Cite this

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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 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.",
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Characterization of the mode of action of Aurodox, a type III secretion system inhibitor from streptomyces goldiniensis. / McHugh, Rebecca E; O'Boyle, Nicky; Connolly, James P R; Hoskisson, Paul A; Roe, Andrew J.

In: Infection and Immunity, Vol. 87, No. 2, e00595-18, 28.02.2019.

Research output: Contribution to journalArticle

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T1 - Characterization of the mode of action of Aurodox, a type III secretion system inhibitor from streptomyces goldiniensis

AU - McHugh, Rebecca E

AU - O'Boyle, Nicky

AU - Connolly, James P R

AU - Hoskisson, Paul A

AU - Roe, Andrew J

N1 - Copyright © 2018 McHugh et al.

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