scholarly journals The Transcriptional Regulator CzcR Modulates Antibiotic Resistance and Quorum Sensing in Pseudomonas aeruginosa

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e38148 ◽  
Author(s):  
Guennaëlle Dieppois ◽  
Véréna Ducret ◽  
Olivier Caille ◽  
Karl Perron
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Transcriptional Regulator

scholarly journals Assessing the Molecular Targets and Mode of Action of Furanone C-30 on Pseudomonas aeruginosa Quorum Sensing

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1620
Author(s):  
Victor Markus ◽  
Karina Golberg ◽  
Kerem Teralı ◽  
Nazmi Ozer ◽  
Esti Kramarsky-Winter ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Conformational Changes ◽  
Mode Of Action ◽  
Pathogenic Bacteria ◽  
Molecular Targets ◽  
Resistant Bacteria ◽  
Public Healthcare ◽  
C 30

Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe. Pseudomonas aeruginosa is one of the most frequent multidrug-resistant bacteria that utilize QS to control virulence. Many natural compounds, including furanones, have demonstrated strong inhibitory effects on several pathogens via blocking or attenuating QS. While the natural furanones show no activity against P. aeruginosa, furanone C-30, a brominated derivative of natural furanone compounds, has been reported to be a potent inhibitor of the QS system of the notorious opportunistic pathogen. In the present study, we assess the molecular targets and mode of action of furanone C-30 on P. aeruginosa QS system. Our results suggest that furanone C-30 binds to LasR at the ligand-binding site but fails to establish interactions with the residues crucial for the protein’s productive conformational changes and folding, thus rendering the protein dysfunctional. We also show that furanone C-30 inhibits RhlR, independent of LasR, suggesting a complex mechanism for the agent beyond what is known to date.

scholarly journals Revisiting the quorum-sensing hierarchy in Pseudomonas aeruginosa: the transcriptional regulator RhlR regulates LasR-specific factors

Microbiology ◽  
2009 ◽  
Vol 155 (3) ◽  
pp. 712-723 ◽  
Author(s):  
Valérie Dekimpe ◽  
Eric Déziel
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Transcriptional Regulator ◽  
Homoserine Lactone ◽  
The Other ◽  
Virulence Determinants ◽  
Late Stationary Phase ◽  
Regulatory Systems ◽  
Specific Factors

Pseudomonas aeruginosa uses the two major quorum-sensing (QS) regulatory systems las and rhl to modulate the expression of many of its virulence factors. The las system is considered to stand at the top of the QS hierarchy. However, some virulence factors such as pyocyanin have been reported to still be produced in lasR mutants under certain conditions. Interestingly, such mutants arise spontaneously under various conditions, including in the airways of cystic fibrosis patients. Using transcriptional lacZ reporters, LC/MS quantification and phenotypic assays, we have investigated the regulation of QS-controlled factors by the las system. Our results show that activity of the rhl system is only delayed in a lasR mutant, thus allowing the expression of multiple virulence determinants such as pyocyanin, rhamnolipids and C4-homoserine lactone (HSL) during the late stationary phase. Moreover, at this stage, RhlR is able to overcome the absence of the las system by activating specific LasR-controlled functions, including production of 3-oxo-C12-HSL and Pseudomonas quinolone signal (PQS). P. aeruginosa is thus able to circumvent the deficiency of one of its QS systems by allowing the other to take over. This work demonstrates that the QS hierarchy is more complex than the model simply presenting the las system above the rhl system.

scholarly journals Antimicrobial Resistance and Biofilm Formation of Pseudomonas aeruginosa

10.3823/846 ◽  
2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Abdelraouf A Elmanama ◽  
Suhaila Al-Sheboul ◽  
Renad I Abu-Dan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Quorum Sensing ◽  
Bacterial Adhesion ◽  
Biofilm Formation ◽  
Bacterial Infections ◽  
Developmental Stages ◽  
Infection Site ◽  
Major Virulence Factor

Abstract Pseudomonas aeruginosa threatens patient’s care. It is considered as the most complicated health care associated pathogen to be eliminated from infection site. The biofilm forming ability of P. aeruginosa, being a major virulence factor for most pathogenic microorganism, protects it from host immunity and contribute to antibiotic resistance of this organism. It is estimated that about 80% of infectious diseases are due to biofilm mode of growth. Biofilm forming ability of bacteria imparts antimicrobial resistance that leads to many persistent and chronic bacterial infections. The world is becoming increasingly under the threat of entering the “post-antibiotic era”, an era in which the rate of death from bacterial infections is higher than from cancer. This review focus on P. aeruginosa biofilm forming ability; definition, developmental stages, and significance. In addition, the quorum sensing and the antibiotic resistance of this pathogen is discussed. Keywords: Biofilm; bacterial adhesion; Pseudomonas aeruginosa; antimicrobial resistance; quorum sensing.

scholarly journals Antibiotic Resistance Evolution Is Contingent on the Quorum-Sensing Response in Pseudomonas aeruginosa

2019 ◽  
Vol 36 (10) ◽  
pp. 2238-2251 ◽  
Author(s):  
Sara Hernando-Amado ◽  
Fernando Sanz-García ◽  
José Luis Martínez
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Wild Type ◽  
Resistance Mutations ◽  
Epistatic Interactions ◽  
Adaptive Mutations ◽  
Resistance Evolution ◽  
Evolutionary Trajectories

Abstract Different works have explored independently the evolution toward antibiotic resistance and the role of eco-adaptive mutations in the adaptation to a new habitat (as the infected host) of bacterial pathogens. However, knowledge about the connection between both processes is still limited. We address this issue by comparing the evolutionary trajectories toward antibiotic resistance of a Pseudomonas aeruginosa lasR defective mutant and its parental wild-type strain, when growing in presence of two ribosome-targeting antibiotics. Quorum-sensing lasR defective mutants are selected in P. aeruginosa populations causing chronic infections. Further, we observed they are also selected in vitro as a first adaptation for growing in culture medium. By using experimental evolution and whole-genome sequencing, we found that the evolutionary trajectories of P. aeruginosa in presence of these antibiotics are different in lasR defective and in wild-type backgrounds, both at the phenotypic and the genotypic levels. Recreation of a set of mutants in both genomic backgrounds (either wild type or lasR defective) allowed us to determine the existence of negative epistatic interactions between lasR and antibiotic resistance determinants. These epistatic interactions could lead to mutual contingency in the evolution of antibiotic resistance when P. aeruginosa colonizes a new habitat in presence of antibiotics. If lasR mutants are selected first, this would constraint antibiotic resistance evolution. Conversely, when resistance mutations (at least those studied in the present work) are selected, lasR mutants may not be selected in presence of antibiotics. These results underlie the importance of contingency and epistatic interactions in modulating antibiotic resistance evolution.

scholarly journals Environmental Regulation of Pseudomonas aeruginosa PAO1 Las and Rhl Quorum-Sensing Systems

2007 ◽  
Vol 189 (13) ◽  
pp. 4827-4836 ◽  
Author(s):  
Kangmin Duan ◽  
Michael G. Surette
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Environmental Conditions ◽  
Transcriptional Regulator ◽  
Transcriptional Regulators ◽  
Growth Conditions ◽  
Fine Tuning ◽  
Relative Timing ◽  
Sensing Systems ◽  
Two Systems

ABSTRACT The lasI-lasR and the rhlI-rhlR quorum-sensing systems in Pseudomonas aeruginosa regulate the expression of numerous cellular and secreted virulence factor genes and play important roles in the development of biofilms. The las and rhl systems themselves are known to be directly or indirectly regulated by a number of transcriptional regulators, and consequently, their expression is sensitive to environmental conditions. In this report, the activities of these two quorum-sensing systems have been examined systematically under 46 growth conditions, and the regulation by environmental conditions has been investigated. The relative timing and strength of expression of these two systems varied significantly under different conditions, which contrasts with the notion of a preset hierarchy with these two systems in P. aeruginosa. Depending on the growth conditions, the correlation between each synthase and its cognate transcriptional regulator also varied, suggesting that the transcription of these genes independently allows for further fine tuning of each system. Finally, we observe that the activities of both the lasI-lasR and the rhlI-rhlR quorum-sensing systems were dramatically enhanced in the presence of extracts of sputum samples from cystic fibrosis patients.

A new quorum-sensing inhibitor attenuates virulence and decreases antibiotic resistance in Pseudomonas aeruginosa

2012 ◽  
Vol 50 (6) ◽  
pp. 987-993 ◽  
Author(s):  
Yu-Xiang Yang ◽  
Zhen-Hua Xu ◽  
Yu-Qian Zhang ◽  
Jing Tian ◽  
Li-Xing Weng ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Quorum Sensing Inhibitor

scholarly journals The Pseudomonas aeruginosa rmlBDAC operon, encoding dTDP-l-rhamnose biosynthetic enzymes, is regulated by the quorum-sensing transcriptional regulator RhlR and the alternative sigma factor σS

Microbiology ◽  
2012 ◽  
Vol 158 (4) ◽  
pp. 908-916 ◽  
Author(s):  
Marisela Aguirre-Ramírez ◽  
Gerardo Medina ◽  
Abigail González-Valdez ◽  
Victoria Grosso-Becerra ◽  
Gloria Soberón-Chávez
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Sigma Factor ◽  
Transcriptional Regulator ◽  
Alternative Sigma Factor ◽  
Biosynthetic Enzymes

scholarly journals The analysis of the role of MexAB-OprM on quorum sensing homeostasis shows that the apparent redundancy of Pseudomonas aeruginosa multidrug efflux pumps allows keeping the robustness and the plasticity of this intercellular signaling network

2020 ◽  
Author(s):  
Manuel Alcalde-Rico ◽  
Jorge Olivares-Pacheco ◽  
Nigel Halliday ◽  
Miguel Cámara ◽  
José Luis Martínez
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Multidrug Efflux ◽  
Intrinsic Resistance ◽  
Bacterial Physiology ◽  
Multidrug Efflux Pumps ◽  
Depth Analysis

AbstractMultidrug efflux pumps are key determinants for antibiotic resistance. Besides contributing to intrinsic resistance, their overexpression is frequently a cause of the increased resistance acquired during therapy. In addition to their role in resistance to antimicrobials, efflux pumps are ancient and conserved elements with relevant roles in different aspects of the bacterial physiology. It is then conceivable that their overexpression might cause a burden that will be translated into a fitness cost associated with the acquisition of resistance. In the case of Pseudomonas aeruginosa, it has been stated that overexpression of different efflux pumps is linked to the impairment of the quorum sensing (QS) response. Nevertheless, the causes of such impairment are different for each analyzed efflux pump. In this study, we performed an in-depth analysis of the QS-mediated response of a P. aeruginosa antibiotic resistant mutant that overexpresses MexAB-OprM. Although previous work claimed that this efflux pump extrudes the QS signal 3-oxo-C12-HSL, we show otherwise. Our results suggest that the observed attenuation in the QS response when overexpressing this pump is related to a reduced availability of intracellular octanoate, one of the precursors of the biosynthesis of alkyl quinolone QS signals. The overexpression of other P. aeruginosa efflux pumps has been shown to also cause a reduction in intracellular levels of QS signals or their precursors impacting on these signaling mechanisms. However, the molecules involved are distinct for each efflux pump, indicating that they can differentially contribute to the P. aeruginosa quorum sensing homeostasis.ImportanceThe success of bacterial pathogens to cause disease relies on their virulence capabilities as well as in their resistance to antibiotic interventions. In the case of the important nosocomial pathogen Pseudomonas aeruginosa, multidrug efflux pumps participate in the resistance/virulence crosstalk since, besides contributing to antibiotic resistance, they can also modulate the quorum sensing (QS) response. We show that mutants overexpressing the MexAB-OprM efflux pump, present an impaired QS response due to the reduced availability of the QS signal precursor octanoate, not because they extrude, as previously stated, the QS signal 3-oxo-C12-HSL. Together with previous studies, this indicates that, although the consequences of overexpressing efflux pumps are similar (impaired QS response), the mechanisms are different. This ‘apparent redundancy’ of RND efflux systems can be understood as a P. aeruginosa strategy to keep the robustness of the QS regulatory network and modulate its output in response to different signals.

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