Aurodox inhibits type III secretion in multiple Gram-negative pathogens (original) (raw)
Mark, David R. 
ORCID: https://orcid.org/0000-0002-1688-5224, O'Boyle, Nicky, Wale, Kabo Ronald, Tucker, Samantha K., McHugh, Rebecca E. ORCID: https://orcid.org/0000-0003-4664-6125 and Roe, Andrew J. ORCID: https://orcid.org/0000-0003-3698-6134(2024) Aurodox inhibits type III secretion in multiple Gram-negative pathogens.Open Biology, 14(11), 240240. (doi: 10.1098/rsob.240240) (PMID:39591989) (PMCID:PMC11597412)
Abstract
Gram-negative pathogens pose a significant threat due to their propensity for causing various infections, often coupled with formidable resistance to conventional antibiotic treatments. The development of antivirulence (AV) compounds emerges as a promising alternative strategy by disrupting virulence mechanisms rather than targeting bacterial viability. Aurodox has exhibited promising AV properties in previous studies by blocking the expression and function of the LEE-encoded type 3 secretion system (T3SS) in enterohaemorrhagic Escherichia coli, an injectosome that translocates effector proteins directly into host target cells. However, aurodox’s efficacy against the T3SS of other pathogens remained unanswered. Using quantitative real-time polymerase chain reaction, we show that aurodox exerts inhibitory effects on selected T3SS including those of Salmonella Typhimurium, Yersinia pseudotuberculosis and Vibrio parahaemolyticus. Imaging of RAW 264.7 cells infected with S. Typhimurium showed that aurodox protects against late stages of infection by blocking the expression of the SPI-2 T3SS. To elucidate a conserved mechanism of action, we compared transcriptomic datasets from both E. coli and S. Typhimurium treated with aurodox to identify orthologous genes differentially expressed in response to aurodox treatment across both pathogens. This study sheds light on potential mechanisms driving the action of this promising AV compound.
| Item Type: | Articles |
|---|---|
| Additional Information: | We would like to acknowledge funding from the Wellcome Trust CIC scheme for funding work by DM and NOB and the Wellcome Trust IIB PhD Scheme for funding SKT. The Medical Research Council (MR/V011499/1) funded REM and AJR. |
| Keywords: | Aurodox, polyketide, virulence, type three secretion system, infection. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Roe, Professor Andrew and Wale, Kabo Ronald and McHugh, Dr Rebecca and Tucker, Ms Samantha and Mark, Dr David |
| Creator Roles: | Mark, D.Data curation, Formal analysis, Investigation, Validation, Writing – original draftWale, K. R.Formal analysis, Writing – review and editingTucker, S.Formal analysis, Writing – review and editingMcHugh, R.Investigation, Supervision, Writing – original draftRoe, A.Conceptualization, Funding acquisition, Project administration, Supervision, Writing – original draft, Writing – review and editing |
| Authors: | Mark, D. R., O'Boyle, N., Wale, K. R., Tucker, S. K., McHugh, R. E., and Roe, A. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Open Biology |
| Publisher: | The Royal Society |
| ISSN: | 2046-2441 |
| ISSN (Online): | 2046-2441 |
| Copyright Holders: | Copyright © 2024 The Author(s) |
| First Published: | First published in Open Biology 14:240240 |
| Publisher Policy: | Reproduced under a creative commons licence |
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Funder and Project Information
Aversion Therapy for Bacteria: Repurposing Aurodox
Andrew Roe
MR/V011499/1
Chemistry
Deposit and Record Details
| ID Code: | 340043 |
|---|---|
| Depositing User: | Mr Matt Mahon |
| Datestamp: | 28 Oct 2024 09:33 |
| Last Modified: | 12 Dec 2024 13:04 |
| Date of acceptance: | 24 October 2024 |
| Date of first online publication: | 27 November 2024 |
| Date Deposited: | 28 October 2024 |
| Data Availability Statement: | Yes |