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Characterization of the mode of action of aurodox, a type III secretion system inhibitor from Streptomyces goldiniensis

Lookup NU author(s): Dr James ConnollyORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

Copyright © 2019 McHugh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.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.

Publication metadata

Author(s): McHugh RE, O'Boyle N, Connolly JPR, Hoskisson PA, Roe AJ

Publication type: Article

Publication status: Published

Journal: Infection and Immunity

Year: 2019

Volume: 87

Issue: 2

Print publication date: 01/02/2019

Online publication date: 24/01/2019

Acceptance date: 12/11/2018

Date deposited: 25/09/2019

ISSN (print): 0019-9567

ISSN (electronic): 1098-5522

Publisher: American Society for Microbiology

URL: https://doi.org/10.1128/IAI.00595-18

DOI: 10.1128/IAI.00595-18

PubMed id: 30455200

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