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

Syed Ahmed, Michelle Rudden, Thomas J. Smyth, J Dooley, R Marchant, Ibrahim Banat

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.
LanguageEnglish
Pages3521-3535
Number of pages15
JournalApplied Microbiology and Biotechnology
Volume103
Issue number8
Early online date9 Mar 2019
DOIs
Publication statusPublished - 1 Apr 2019

Fingerprint

Quorum Sensing
Virulence Factors
Pseudomonas aeruginosa
Virulence
Down-Regulation
Gene Expression
Salicylic Acid
Pyocyanine
Pancreatic Elastase
Phytochemicals
Regulator Genes
Biofilms
Metabolic Networks and Pathways
Pharmaceutical Preparations
Peptide Hydrolases
Anti-Bacterial Agents
Bacteria
Phenotype
Growth
Infection

Keywords

  • Trans-cinnamaldehyde
  • Salicylic acid
  • Quorum sensing
  • Quorum sensing inhibitor
  • Pseudomonas aeruginosa

Cite this

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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 naturallyisolated 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 QSIssignificantly 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 showsthe significant inhibitory effect of natural plant-derived compounds on the repression of QS systems in P. aeruginosa.",
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Natural quorum sensing inhibitors effectively downregulate gene expression of Pseudomonas aeruginosa virulence factors. / Ahmed, Syed; Rudden, Michelle; Smyth, Thomas J.; Dooley, J; Marchant, R; Banat, Ibrahim.

In: Applied Microbiology and Biotechnology, Vol. 103, No. 8, 01.04.2019, p. 3521-3535.

Research output: Contribution to journalArticle

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