scholarly journals Quorum Quenching Enzymes and Their Application in Degrading Signal Molecules to Block Quorum Sensing-Dependent Infection

2013 ◽  
Vol 14 (9) ◽  
pp. 17477-17500 ◽  
Author(s):  
Fang Chen ◽  
Yuxin Gao ◽  
Xiaoyi Chen ◽  
Zhimin Yu ◽  
Xianzhen Li
Keyword(s):  
Quorum Sensing ◽  
Quorum Quenching ◽  
Signal Molecules

scholarly journals Interference with Pseudomonas aeruginosa Quorum Sensing and Virulence by the Mycobacterial Pseudomonas Quinolone Signal Dioxygenase AqdC in Combination with the N-Acylhomoserine Lactone Lactonase QsdA

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Franziska S. Birmes ◽  
Ruth Säring ◽  
Miriam C. Hauke ◽  
Niklas H. Ritzmann ◽  
Steffen L. Drees ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Rhodococcus Erythropolis ◽  
Quorum Quenching ◽  
Signal Molecules ◽  
Content Type ◽  
Acylhomoserine Lactone ◽  
Regulatory Effects ◽  
Epithelial Lung Cells

ABSTRACT The nosocomial pathogen Pseudomonas aeruginosa regulates its virulence via a complex quorum sensing network, which, besides N-acylhomoserine lactones, includes the alkylquinolone signal molecules 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal [PQS]) and 2-heptyl-4(1H)-quinolone (HHQ). Mycobacteroides abscessus subsp. abscessus, an emerging pathogen, is capable of degrading the PQS and also HHQ. Here, we show that although M. abscessus subsp. abscessus reduced PQS levels in coculture with P. aeruginosa PAO1, this did not suffice for quenching the production of the virulence factors pyocyanin, pyoverdine, and rhamnolipids. However, the levels of these virulence factors were reduced in cocultures of P. aeruginosa PAO1 with recombinant M. abscessus subsp. massiliense overexpressing the PQS dioxygenase gene aqdC of M. abscessus subsp. abscessus, corroborating the potential of AqdC as a quorum quenching enzyme. When added extracellularly to P. aeruginosa cultures, AqdC quenched alkylquinolone and pyocyanin production but induced an increase in elastase levels. When supplementing P. aeruginosa cultures with QsdA, an enzyme from Rhodococcus erythropolis which inactivates N-acylhomoserine lactone signals, rhamnolipid and elastase levels were quenched, but HHQ and pyocyanin synthesis was promoted. Thus, single quorum quenching enzymes, targeting individual circuits within a complex quorum sensing network, may also elicit undesirable regulatory effects. Supernatants of P. aeruginosa cultures grown in the presence of AqdC, QsdA, or both enzymes were less cytotoxic to human epithelial lung cells than supernatants of untreated cultures. Furthermore, the combination of both aqdC and qsdA in P. aeruginosa resulted in a decline of Caenorhabditis elegans mortality under P. aeruginosa exposure.

scholarly journals Novel Reporter for Identification of Interference with Acyl Homoserine Lactone and Autoinducer-2 Quorum Sensing

2014 ◽  
Vol 81 (4) ◽  
pp. 1477-1489 ◽  
Author(s):  
Nancy Weiland-Bräuer ◽  
Nicole Pinnow ◽  
Ruth A. Schmitz
Keyword(s):  
Quorum Sensing ◽  
Vibrio Fischeri ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Signal Molecules ◽  
Lethal Gene ◽  
Reporter Strain ◽  
Content Type ◽  
E Coli ◽  
Autoinducer 2

ABSTRACTTwo reporter strains were established to identify novel biomolecules interfering with bacterial communication (quorum sensing [QS]). The basic design of theseEscherichia coli-based systems comprises a gene encoding a lethal protein fused to promoters induced in the presence of QS signal molecules. Consequently, theseE. colistrains are unable to grow in the presence of the respective QS signal molecules unless a nontoxic QS-interfering compound is present. The first reporter strain designed to detect autoinducer-2 (AI-2)-interfering activities (AI2-QQ.1) contained theE. coliccdBlethal gene under the control of theE. colilsrApromoter. The second reporter strain (AI1-QQ.1) contained theVibrio fischeriluxIpromoter fused to theccdBgene to detect interference with acyl-homoserine lactones. Bacteria isolated from the surfaces of several marine eukarya were screened for quorum-quenching (QQ) activities using the established reporter systems AI1-QQ.1 and AI2-QQ.1. Out of 34 isolates, two interfered with acylated homoserine lactone (AHL) signaling, five interfered with AI-2 QS signaling, and 10 were demonstrated to interfere with both signal molecules. Open reading frames (ORFs) conferring QQ activity were identified for three selected isolates (Photobacteriumsp.,Pseudoalteromonassp., andVibrio parahaemolyticus). Evaluation of the respective heterologously expressed and purified QQ proteins confirmed their ability to interfere with the AHL and AI-2 signaling processes.

scholarly journals Quorum Quenching by an N-Acyl-Homoserine Lactone Acylase from Pseudomonas aeruginosa PAO1

2006 ◽  
Vol 74 (3) ◽  
pp. 1673-1682 ◽  
Author(s):  
Charles F. Sio ◽  
Linda G. Otten ◽  
Robbert H. Cool ◽  
Stephen P. Diggle ◽  
Peter G. Braun ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Side Chain ◽  
Signal Molecules ◽  
Acyl Homoserine Lactone ◽  
Beta Lactam ◽  
Signal Molecule ◽  
Pathogenic Potential

ABSTRACT The virulence of the opportunistic human pathogen Pseudomonas aeruginosa PAO1 is controlled by an N-acyl-homoserine lactone (AHL)-dependent quorum-sensing system. During functional analysis of putative acylase genes in the P. aeruginosa PAO1 genome, the PA2385 gene was found to encode an acylase that removes the fatty acid side chain from the homoserine lactone (HSL) nucleus of AHL-dependent quorum-sensing signal molecules. Analysis showed that the posttranslational processing of the acylase and the hydrolysis reaction type are similar to those of the beta-lactam acylases, strongly suggesting that the PA2385 protein is a member of the N-terminal nucleophile hydrolase superfamily. In a bioassay, the purified acylase was shown to degrade AHLs with side chains ranging in length from 11 to 14 carbons at physiologically relevant low concentrations. The substituent at the 3′ position of the side chain did not affect activity, indicating broad-range AHL quorum-quenching activity. Of the two main AHL signal molecules of P. aeruginosa PAO1, N-butanoyl-l-homoserine lactone (C4-HSL) and N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL), only 3-oxo-C12-HSL is degraded by the enzyme. Addition of the purified protein to P. aeruginosa PAO1 cultures completely inhibited accumulation of 3-oxo-C12-HSL and production of the signal molecule 2-heptyl-3-hydroxy-4(1H)-quinolone and reduced production of the virulence factors elastase and pyocyanin. Similar results were obtained when the PA2385 gene was overexpressed in P. aeruginosa. These results demonstrate that the protein has in situ quorum-quenching activity. The quorum-quenching AHL acylase may enable P. aeruginosa PAO1 to modulate its own quorum-sensing-dependent pathogenic potential and, moreover, offers possibilities for novel antipseudomonal therapies.

scholarly journals Quenching of acyl-homoserine lactone-dependent quorum sensing by enzymatic disruption of signal molecules.

2009 ◽  
Vol 56 (1) ◽  
Author(s):  
Robert Czajkowski ◽  
Sylwia Jafra
Keyword(s):  
Quorum Sensing ◽  
Pathogenic Bacteria ◽  
Degradation Products ◽  
Antibiotic Production ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Signal Molecules ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Animal Pathogens

Many Gram-positive and Gram-negative bacteria communicate using small diffusible signal molecules called autoinducers. This process, known as quorum sensing (QS), links cell density to the expression of genes as diverse as those associated with virulence factors production of plant and animal pathogens, bioluminescence, antibiotic production, sporulation or biofilm formation. In Gram-negative bacteria, this communication is mainly mediated by N-acyl-homoserine lactones (AHLs). It has been proven that inactivation of the signal molecules attenuates many of the processes controlled by QS. Enzymatic degradation of the signal molecules has been amply described. Two main classes of AHL-inactivating enzymes were identified: AHL lactonases which hydrolyse the lactone ring in AHLs, and AHL acylases (syn. AHL amidases) which liberate a free homoserine lactone and a fatty acid. Recently, AHL oxidoreductase, a novel type of AHL inactivating enzyme, was described. The activity of these enzymes results in silencing the QS-regulated processes, as degradation products cannot act as signal molecules. The ability to inactivate AHL (quorum quenching, QQ) might be useful in controlling virulence of many pathogenic bacteria.

scholarly journals Quorum Sensing Pseudomonas Quinolone Signal Forms Chiral Supramolecular Assemblies With the Host Defense Peptide LL-37

2021 ◽  
Vol 8 ◽  
Author(s):  
Ferenc Zsila ◽  
Maria Ricci ◽  
Imola Csilla Szigyártó ◽  
Priyanka Singh ◽  
Tamás Beke-Somfai
Keyword(s):  
Quorum Sensing ◽  
Host Defense ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Quorum Quenching ◽  
Bacterial Biofilms ◽  
Phenotypic Traits ◽  
Signal Molecules ◽  
Supramolecular Architectures

Host defense antimicrobial peptides (HDPs) constitute an integral component of the innate immune system having nonspecific activity against a broad spectrum of microorganisms. They also have diverse biological functions in wound healing, angiogenesis, and immunomodulation, where it has also been demonstrated that they have a high affinity to interact with human lipid signaling molecules. Within bacterial biofilms, quorum sensing (QS), the vital bacterial cell-to-cell communication system, is maintained by similar diffusible small molecules which control phenotypic traits, virulence factors, biofilm formation, and dispersion. Efficient eradication of bacterial biofilms is of particular importance as these colonies greatly help individual cells to tolerate antibiotics and develop antimicrobial resistance. Regarding the antibacterial function, for several HDPs, including the human cathelicidin LL-37, affinity to eradicate biofilms can exceed their activity to kill individual bacteria. However, related underlying molecular mechanisms have not been explored yet. Here, we employed circular dichroism (CD) and UV/VIS spectroscopic analysis, which revealed that LL-37 exhibits QS signal affinity. This archetypal representative of HDPs interacts with the Pseudomonas quinolone signal (PQS) molecules, producing co-assemblies with peculiar optical activity. The binding of PQS onto the asymmetric peptide chains results in chiral supramolecular architectures consisting of helically disposed, J-aggregated molecules. Besides the well-known bacterial membrane disruption activity, our data propose a novel action mechanism of LL-37. As a specific case of the so-called quorum quenching, QS signal molecules captured by the peptide are sequestered inside co-assemblies, which may interfere with the microbial QS network helping to prevent and eradicate bacterial infections.

scholarly journals Widespread Existence of Quorum Sensing Inhibitors in Marine Bacteria: Potential Drugs to Combat Pathogens with Novel Strategies

Marine Drugs ◽  
2019 ◽  
Vol 17 (5) ◽  
pp. 275 ◽  
Author(s):  
Jing Zhao ◽  
Xinyun Li ◽  
Xiyan Hou ◽  
Chunshan Quan ◽  
Ming Chen
Keyword(s):  
Quorum Sensing ◽  
Marine Environment ◽  
Marine Bacteria ◽  
Regulatory Protein ◽  
Virulence Gene ◽  
Quorum Quenching ◽  
Signal Molecules ◽  
Terrestrial Environment ◽  
Virulence Gene Expression ◽  
Novel Strategy

Quorum sensing (QS) is a phenomenon of intercellular communication discovered mainly in bacteria. A QS system consisting of QS signal molecules and regulatory protein components could control physiological behaviors and virulence gene expression of bacterial pathogens. Therefore, QS inhibition could be a novel strategy to combat pathogens and related diseases. QS inhibitors (QSIs), mainly categorized into small chemical molecules and quorum quenching enzymes, could be extracted from diverse sources in marine environment and terrestrial environment. With the focus on the exploitation of marine resources in recent years, more and more QSIs from the marine environment have been investigated. In this article, we present a comprehensive review of QSIs from marine bacteria. Firstly, screening work of marine bacteria with potential QSIs was concluded and these marine bacteria were classified. Afterwards, two categories of marine bacteria-derived QSIs were summarized from the aspects of sources, structures, QS inhibition mechanisms, environmental tolerance, effects/applications, etc. Next, structural modification of natural small molecule QSIs for future drug development was discussed. Finally, potential applications of QSIs from marine bacteria in human healthcare, aquaculture, crop cultivation, etc. were elucidated, indicating promising and extensive application perspectives of QS disruption as a novel antimicrobial strategy.

scholarly journals Quorum alleviating Molecules- A Review

2020 ◽  
Vol 6 (12) ◽  
pp. 82-86
Author(s):  
Dr. NohaLaj Dr. Raishy R Hussain and Abhinsha Z
Keyword(s):  
Quorum Sensing ◽  
Protein A ◽  
Quorum Quenching ◽  
Receptor Protein ◽  
Signal Molecules ◽  
Synthetic Analogue ◽  
Cognate Receptor ◽  
Competitive Inhibitors ◽  
Type Receptor ◽  
Basic Similarity

The hindrance of quorum sensing is generally indicated to as quorum quenching. A few compounds have been combined to intrude on quorum sensing articulation by echoing AHL particles, N-acyl-3-amino-5H furanone, a synthetic analogue of N-AHL viably keeps the receipt of signal atom by obstructing its receptor Lux R protein. AHL controlled quorum sensing can be distressed by various methods, for example, lessening the movement of AHL cognate receptor protein or AHL synthase, hindering the creation of QS signal molecules, degradation of the AHL, and mimicking the signal atoms by utilizing their synthetic analogs. Additionally, obstruction of sensing signal transduction can be accomplished by utilizing an opponent particle equipped for contending or meddling with the local AHL motion for endorsed entry to the LUXR-type receptor. Competitive inhibitors are basically like the local AHL signal and can bind to and involve the AHL restricting site yet will fail to enact the LuxR-type receptor. The non-competitive inhibitors indicate almost no basic similarity to AHL signals and these particles bind to various locales on the receptor protein. A variety of natural Quorum quenching molecules have been identified.

scholarly journals Acinetobacter baumannii Quorum sensing: A way to communicate and a target to eradicate

2021 ◽  
Vol 3 (2) ◽  
pp. 134-145
Author(s):  
Elkheloui Raja ◽  
Hamadi Fatima ◽  
Mimouni Rachida
Keyword(s):  
Quorum Sensing ◽  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Quorum Quenching ◽  
Signal Molecules ◽  
Gram Negative Bacteria ◽  
Chronic Infections ◽  
New Strategy

Quorum sensing is a communication system based on the actions of chemical signal molecules depending on the density of the cell population. These molecules are widely considered as effectors of the gene expression of several virulence factors. As a result, it has attracted a lot of attention because of its possible applicability as a target for treating infections. This review attempts to give a description of this system on gram negative bacteria specifically on Acinetobacter baumannii as an important nosocomial pathogen. Additionally, quorum sensing in biofilm will be also treated because it is considered as the origin of several chronic infections. Numerous studies have been carried out to prove the role of inhibitors in the disruption of quorum sensing, known as quorum quenching. Quorum quenching is a new strategy to eradicate bacterial infections due to the crucial intervention of quorum sensing in different virulence factors and particularly in the biofilm formation.

scholarly journals A Bacterial Tower of Babel: Quorum-Sensing Signaling Diversity and Its Evolution

2020 ◽  
Vol 74 (1) ◽  
pp. 587-606 ◽  
Author(s):  
Nitzan Aframian ◽  
Avigdor Eldar
Keyword(s):  
Quorum Sensing ◽  
Social Interactions ◽  
Signal Molecules ◽  
Allelic Polymorphism ◽  
Dependent Manner ◽  
Tower Of Babel ◽  
Cognate Receptor ◽  
Wide Range ◽  
Family Code ◽  
Bacterial Groups

Quorum sensing is a process in which bacteria secrete and sense a diffusible molecule, thereby enabling bacterial groups to coordinate their behavior in a density-dependent manner. Quorum sensing has evolved multiple times independently, utilizing different molecular pathways and signaling molecules. A common theme among many quorum-sensing families is their wide range of signaling diversity—different variants within a family code for different signal molecules with a cognate receptor specific to each variant. This pattern of vast allelic polymorphism raises several questions—How do different signaling variants interact with one another? How is this diversity maintained? And how did it come to exist in the first place? Here we argue that social interactions between signaling variants can explain the emergence and persistence of signaling diversity throughout evolution. Finally, we extend the discussion to include cases where multiple diverse systems work in concert in a single bacterium.

scholarly journals Peptide signaling without feedback in signal production operates as a true quorum sensing communication system in Bacillus subtilis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Iztok Dogsa ◽  
Mihael Spacapan ◽  
Anna Dragoš ◽  
Tjaša Danevčič ◽  
Žiga Pandur ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacillus Subtilis ◽  
Quorum Sensing ◽  
Cell Density ◽  
Communication System ◽  
Communication Systems ◽  
Feedback Loop ◽  
Signal Molecules ◽  
Specific Cell ◽  
Sharp Transition

AbstractBacterial quorum sensing (QS) is based on signal molecules (SM), which increase in concentration with cell density. At critical SM concentration, a variety of adaptive genes sharply change their expression from basic level to maximum level. In general, this sharp transition, a hallmark of true QS, requires an SM dependent positive feedback loop, where SM enhances its own production. Some communication systems, like the peptide SM-based ComQXPA communication system of Bacillus subtilis, do not have this feedback loop and we do not understand how and if the sharp transition in gene expression is achieved. Based on experiments and mathematical modeling, we observed that the SM peptide ComX encodes the information about cell density, specific cell growth rate, and even oxygen concentration, which ensure power-law increase in SM production. This enables together with the cooperative response to SM (ComX) a sharp transition in gene expression level and this without the SM dependent feedback loop. Due to its ultra-sensitive nature, the ComQXPA can operate at SM concentrations that are 100–1000 times lower than typically found in other QS systems, thereby substantially reducing the total metabolic cost of otherwise expensive ComX peptide.

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