Characterisation of the mode of action of Aurodox, a Type III secretion system inhibitor from Streptomyces goldiniensis

McHugh, R. E., O'Boyle, N., Connolly, J. P.R., Hoskisson, P. A. and Roe, A. J. (2019) Characterisation of the mode of action of Aurodox, a Type III secretion system inhibitor from Streptomyces goldiniensis. Infection and Immunity, 87(2), e00595-18. (doi: 10.1128/IAI.00595-18) (PMID:30455200) (PMCID:PMC6346137)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McHugh, Rebecca and Connolly, Dr James and Roe, Professor Andrew and O'Boyle, Dr Nicky
Authors: McHugh, R. E., O'Boyle, N., Connolly, J. P.R., Hoskisson, P. A., and Roe, A. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Infection and Immunity
Publisher:American Society for Microbiology
ISSN:0019-9567
ISSN (Online):1098-5522
Published Online:19 November 2018
Copyright Holders:Copyright © 2018 McHugh et al.
First Published:First published in Infection and Immunity 87(2): e00595-18
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
691101Where and Why: The Influence of Host Metabolism on Bacterial Niche SpecificityAndrew RoeBiotechnology and Biological Sciences Research Council (BBSRC)BB/M029646/1III - BACTERIOLOGY
3002800The Role of Dietary D-serine in Health and DiseaseAndrew RoeBiotechnology and Biological Sciences Research Council (BBSRC)BB/R006539/1III - Bacteriology