Characterization of the Mode of Action of Aurodox, a Type III Secretion System Inhibitor from Streptomyces goldiniensis.

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 downregulates 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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

McHugh RE,O'Boyle N,Connolly JPR,Hoskisson PA,Roe AJ

doi

10.1128/IAI.00595-18

subject

Has Abstract

pub_date

2019-01-24 00:00:00

issue

2

eissn

0019-9567

issn

1098-5522

pii

IAI.00595-18

journal_volume

87

pub_type

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