Ahmed, Syed A K S, Rudden, Michelle orcid.org/0000-0001-9617-087X, Smyth, Thomas J et al. (3 more authors) (2019) Natural quorum sensing inhibitors effectively downregulate gene expression of Pseudomonas aeruginosa virulence factors. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY. pp. 3521-3535. ISSN 0175-7598
Abstract
At present, anti-virulence drugs are being considered as potential therapeutic alternatives and/or adjuvants to currently failing antibiotics. These drugs do not kill bacteria but inhibit virulence factors essential for establishing infection and pathogenesis through targeting non-essential metabolic pathways reducing the selective pressure to develop resistance. We investigated the effect of naturally isolated plant compounds on the repression of the quorum sensing (QS) system which is linked to virulence/pathogenicity in Pseudomonas aeruginosa. Our results show that trans-cinnamaldehyde (CA) and salicylic acid (SA) significantly inhibit expression of QS regulatory and virulence genes in P. aeruginosa PAO1 at sub-inhibitory levels without any bactericidal effect. CA effectively downregulated both the las and rhl QS systems with lasI and lasR levels inhibited by 13- and 7-fold respectively compared to 3- and 2-fold reductions with SA treatment, during the stationary growth phase. The QS inhibitors (QSI) also reduced the production of extracellular virulence factors with CA reducing protease, elastase and pyocyanin by 65%, 22% and 32%, respectively. The QSIs significantly reduced biofilm formation and concomitantly with repressed rhamnolipid gene expression, only trace amount of extracellular rhamnolipids were detected. The QSIs did not completely inhibit virulence factor expression and production but their administration significantly lowered the virulence phenotypes at both the transcriptional and extracellular levels. This study shows the significant inhibitory effect of natural plant-derived compounds on the repression of QS systems in P. aeruginosa.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2019 |
Keywords: | Acrolein/analogs & derivatives,Bacterial Proteins/genetics,Biofilms/drug effects,Extracellular Space/metabolism,Gene Expression Regulation, Bacterial/drug effects,Pseudomonas aeruginosa/drug effects,Quorum Sensing/drug effects,Salicylic Acid/pharmacology,Virulence/drug effects,Virulence Factors/genetics |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 30 Sep 2019 12:50 |
Last Modified: | 21 Jan 2025 17:42 |
Published Version: | https://doi.org/10.1007/s00253-019-09618-0 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1007/s00253-019-09618-0 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:151491 |
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