Natural quorum sensing inhibitors effectively downregulate gene expression of Pseudomonas aeruginosa virulence factors

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 metaboli...

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Veröffentlicht in:Applied microbiology and biotechnology 2019-04, Vol.103 (8), p.3521-3535
Hauptverfasser: Ahmed, Syed A. K. S., Rudden, Michelle, Smyth, Thomas J., Dooley, James S. G., Marchant, Roger, Banat, Ibrahim M.
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container_issue 8
container_start_page 3521
container_title Applied microbiology and biotechnology
container_volume 103
creator Ahmed, Syed A. K. S.
Rudden, Michelle
Smyth, Thomas J.
Dooley, James S. G.
Marchant, Roger
Banat, Ibrahim M.
description 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 .
doi_str_mv 10.1007/s00253-019-09618-0
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subjects Adjuvants
Analysis
antibacterial properties
Antibiotics
bacteria
biochemical pathways
biofilm
Biofilms
Biomedical and Life Sciences
Biotechnology
Cinnamaldehyde
Control
developmental stages
drugs
Elastase
Extracellular levels
Gene expression
gene expression regulation
genes
Genetic aspects
Genomics
Genomics, Transcriptomics, Proteomics
Inhibitors
Life Sciences
Metabolic pathways
Microbial Genetics and Genomics
Microbiology
Pathogenesis
Pathogenicity
Pathogens
phenotype
Phenotypes
Plants
Prevention
Proteomics
Pseudomonas aeruginosa
Pseudomonas aeruginosa infections
Pyocyanin
Quorum sensing
Rhamnolipids
Salicylic acid
System effectiveness
therapeutics
Transcription
transcription (genetics)
Transcriptomics
Virulence
Virulence (Microbiology)
Virulence factors
title Natural quorum sensing inhibitors effectively downregulate gene expression of Pseudomonas aeruginosa virulence factors
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