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.
| Original language | English |
|---|---|
| Article number | e00595-18 |
| Number of pages | 12 |
| Journal | Infection and Immunity |
| Volume | 87 |
| Issue number | 2 |
| Early online date | 24 Jan 2019 |
| DOIs | |
| Publication status | Published - 28 Feb 2019 |
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Keywords
- streptomyces goldiniensis
- aurodox
- citrobacter rodentium
Cite this
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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 journal › Article
TY - JOUR
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.
PY - 2019/2/28
Y1 - 2019/2/28
N2 - 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.
AB - 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.
KW - streptomyces goldiniensis
KW - aurodox
KW - citrobacter rodentium
U2 - 10.1128/IAI.00595-18
DO - 10.1128/IAI.00595-18
M3 - Article
C2 - 30455200
VL - 87
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 2
M1 - e00595-18
ER -