Characterization 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) Characterization 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 is able to block the pathogenesis of the murine pathogen In this work, we aimed to gain a better understanding of the mechanism of action of the compound. We show that Aurodox downregulates the expression of the type III secretion systems of enteropathogenic and enterohemorrhagic Furthermore, we have used transcriptomic analysis to show that Aurodox inhibits the expression at the transcriptional level by repressing the master regulator, Our data support a model in which Aurodox acts upstream of 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.

Item Type:Articles
Additional Information:R.E.M.’s work was funded by the University of Glasgow Medicine, Veterinary and Life Sciences Doctoral Training Partnership and the University of Strathclyde. J.P.R.C., N.O., and A.J.R. are supported by BBSRC funding (BB/M029646/1 and BB/R006539/1).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McHugh, Dr Rebecca
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 > School of Infection & Immunity
Research Group:Andrew J Roe
Journal Name:Infection and Immunity
Journal Abbr.:InfectImmun
Publisher:American Society for Microbiology
ISSN:0019-9567
ISSN (Online):1098-5522
Published Online:12 November 2018
Copyright Holders:Copyright © 2019 The Authors
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
172251Where and Why: The Influence of Host Metabolism on Bacterial Niche SpecificityRichard CogdellBiotechnology and Biological Sciences Research Council (BBSRC)BB/M029646/1School of Infection & Immunity
300280The Role of Dietary D-serine in Health and DiseaseAndrew RoeBiotechnology and Biological Sciences Research Council (BBSRC)BB/R006539/1SII - Bacteriology