scholarly journals The PqsE-RhlR Interaction Regulates RhlR DNA Binding to Control Virulence Factor Production in Pseudomonas aeruginosa

2022 ◽  
Author(s):  
Kayla A. Simanek ◽  
Isabelle R. Taylor ◽  
Erica K. Richael ◽  
Erica Lasek-Nesselquist ◽  
Bonnie L. Bassler ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Dna Binding ◽  
Quorum Sensing ◽  
Virulence Factor ◽  
Cell Communication ◽  
Communication Process ◽  
Collective Behaviors ◽  
Factor Production ◽  
A Cell ◽  
Virulence Factor Production

Bacteria use a cell-cell communication process called quorum sensing (QS) to orchestrate collective behaviors. QS relies on the group-wide detection of molecules called autoinducers (AI).

scholarly journals A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in Pseudomonas aeruginosa

Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1385
Author(s):  
Ahmed Al Saqr ◽  
Mohammed F. Aldawsari ◽  
El-Sayed Khafagy ◽  
Moataz A. Shaldam ◽  
Wael A. H. Hegazy ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Cell Communication ◽  
Factor Production ◽  
In Silico Study ◽  
Liver And Kidney ◽  
Healthcare Associated ◽  
Virulence Factor Production

Pseudomonas aeruginosa can cause a variety of healthcare-associated infections by its arsenal of virulence factors. Virulence factor production is largely controlled by the cell-to-cell communication system termed quorum sensing (QS). Targeting QS may be a good approach to inhibit the production of virulence factors and attenuate pathogenicity without exerting selective stress on bacterial growth. This will greatly reduce the emergence of resistant mutants. In this work, we investigated the anti-virulence and anti-QS activities of the FDA-approved drug allopurinol against the P. aeruginosa PAO1 strain. Allopurinol at 200 µg/mL (1/10 MIC) significantly decreased the production of the QS-controlled Chromobacterium violaceum CV026 violet pigment violacein and other P. aeruginosa QS-controlled virulence factors phenotypically. Furthermore, allopurinol reduced the infiltration of P. aeruginosa and leucocytes and diminished the congestion in the liver and kidney tissues of infected mice. In silico study showed that allopurinol could compete with the autoinducers on binding to the receptors LasR and RhlR by hydrogen bonding. On the molecular level, qRT-PCR proved that allopurinol showed a significant downregulating effect on all tested QS-encoding genes that regulate virulence factor production. In summary, allopurinol is a promising QS inhibitor that may be useful in the future treatment of P. aeruginosa infection.

scholarly journals Quorum-Sensing Antagonistic Activities of Azithromycin in Pseudomonas aeruginosa PAO1: a Global Approach

2006 ◽  
Vol 50 (5) ◽  
pp. 1680-1688 ◽  
Author(s):  
Yusuf Nalca ◽  
Lothar Jänsch ◽  
Florian Bredenbruch ◽  
Robert Geffers ◽  
Jan Buer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factor ◽  
Biofilm Formation ◽  
Great Promise ◽  
Factor Production ◽  
The Impact ◽  
Virulence Factor Production

ABSTRACT The administration of macrolides such as azithromycin for chronic pulmonary infection of cystic fibrosis patients has been reported to be of benefit. Although the mechanisms of action remain obscure, anti-inflammatory effects as well as interference of the macrolide with Pseudomonas aeruginosa virulence factor production have been suggested to contribute to an improved clinical outcome. In this study we used a systematic approach and analyzed the impact of azithromycin on the global transcriptional pattern and the protein expression profile of P. aeruginosa PAO1 cultures versus those in untreated controls. The most remarkable result of this study is the finding that azithromycin exhibited extensive quorum-sensing antagonistic activities. In accordance with the inhibition of the quorum-sensing systems, virulence factor production was diminished and the oxidative stress response was impaired, whereas the type III secretion system was strongly induced. Moreover, P. aeruginosa motility was reduced, which probably accounts for the previously observed impaired biofilm formation capabilities of azithromycin-treated cultures. The interference of azithromycin with quorum-sensing-dependent virulence factor production, biofilm formation, and oxidative stress resistance in P. aeruginosa holds great promise for macrolide therapy in cystic fibrosis. Clearly quorum-sensing antagonist macrolides should be paid more attention in the management of chronic P. aeruginosa infections, and as quorum-sensing antagonists, macrolides might gain vital importance for more general application against chronic infections.

scholarly journals Azithromycin Inhibits Quorum Sensing in Pseudomonas aeruginosa

2001 ◽  
Vol 45 (6) ◽  
pp. 1930-1933 ◽  
Author(s):  
Kazuhiro Tateda ◽  
Rachel Comte ◽  
Jean-Claude Pechere ◽  
Thilo Köhler ◽  
Keizo Yamaguchi ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factor ◽  
Strain Pao1 ◽  
Unknown Mechanism ◽  
Factor Production ◽  
Encoding Gene ◽  
Encoding Genes ◽  
Virulence Factor Production

ABSTRACT We report that 2 μg of azithromycin/ml inhibits the quorum-sensing circuitry of Pseudomonas aeruginosa strain PAO1. Addition of synthetic autoinducers partially restored the expression of the trancriptional activator-encoding geneslasR and rhlR but not that of the autoinducer synthase-encoding gene lasI. We propose that azithromycin interferes with the synthesis of autoinducers, by an unknown mechanism, leading to a reduction of virulence factor production.

scholarly journals Pseudomonas aeruginosa reaches collective decisions via transient segregation of quorum sensing activities across cells

2021 ◽  
Author(s):  
Priyanikha Jayakumar ◽  
Stephen A. Thomas ◽  
Sam P Brown ◽  
Rolf Kuemmerli
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Single Cells ◽  
Cell Communication ◽  
Population Level ◽  
Communication Process ◽  
Fluorescent Reporters ◽  
Induction Pattern ◽  
A Cell

Bacteria engage in a cell-to-cell communication process called quorum sensing (QS) to coordinate expression of cooperative exoproducts at the group level. While population-level QS-responses are well studied, we know little about commitments of single cells to QS. Here, we use flow cytometry to track the investment of Pseudomonas aeruginosa individuals into their intertwined Las and Rhl QS-systems. Using fluorescent reporters, we show that QS gene expression (signal synthase, receptor and exoproduct) was heterogenous and followed a gradual instead of a sharp temporal induction pattern. The simultaneous monitoring of two QS genes revealed that cells transiently segregate into low receptor (lasR) expressers that fully commit to QS, and high receptor expressers that delay QS commitment. Our mathematical model shows that such gene expression segregation could mechanistically be spurred by transcription factor limitation. In evolutionary terms, temporal segregation could serve as a QS-brake to allow for a bet-hedging strategy in unpredictable environments.

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