&lt;p&gt;Quorum Quenching: A Potential Target for Antipseudomonal Therapy&lt;/p&gt;

Hemmati, Fatemeh; Salehi, Roya; Ghotaslou, Reza; Kafil, Hossein Samadi; Hasani, Alka; Gholizadeh, Pourya; Nouri, Roghayeh; Rezaee, Mohammad Ahangarzadeh

doi:10.2147/idr.s263196

Cited by 53 publications

(21 citation statements)

References 167 publications

(291 reference statements)

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“…Furthermore, in the Pa3 isolate, the presence of the carboxypyrano-ant extract caused upregulation of lasR. Because lasR activates the Rhl and Pqs systems [26], it would be expected that its overexpression would lead to upregulation of rhlI, rhlR, and pqsAER, and that was not observed, meaning that an alternative transcription regulator could be responsible for suppressing RhlR and PqsR activation, such as algR or mexT, respectively [46,47].…”

Section: Discussionmentioning

confidence: 98%

Pyranoanthocyanins Interfering with the Quorum Sensing of Pseudomonas aeruginosa and Staphylococcus aureus

Coelho

Oliveira

Fernandes

et al. 2021

IJMS

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Bacterial quorum sensing (QS) is a cell-cell communication system that regulates several bacterial mechanisms, including the production of virulence factors and biofilm formation. Thus, targeting microbial QS is seen as a plausible alternative strategy to antibiotics, with potentiality to combat multidrug-resistant pathogens. Many phytochemicals with QS interference activity are currently being explored. Herein, an extract and a compound of bioinspired origin were tested for their ability to inhibit biofilm formation and interfere with the expression of QS-related genes in Pseudomonas aeruginosa and Staphylococcus aureus. The extract, a carboxypyranoanthocyanins red wine extract (carboxypyrano-ant extract), and the pure compound, carboxypyranocyanidin-3-O-glucoside (carboxypyCy-3-glc), did not cause a visible effect on the biofilm formation of the P. aeruginosa biofilms; however, both significantly affected the formation of biofilms by the S. aureus strains, as attested by the crystal violet assay and fluorescence microscopy. Both the extract and the pure compound significantly interfered with the expression of several QS-related genes in the P. aeruginosa and S. aureus biofilms, as per reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results. Indeed, it was possible to conclude that these molecules interfere with QS at distinct stages and in a strain-specific manner. An extract with anti-QS properties could be advantageous because it is easily obtained and could have broad, antimicrobial therapeutic applications if included in topical formulations.

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Section: Discussionmentioning

confidence: 98%

Pyranoanthocyanins Interfering with the Quorum Sensing of Pseudomonas aeruginosa and Staphylococcus aureus

Coelho

Oliveira

Fernandes

et al. 2021

IJMS

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“…Examples of autoinducers are Nacyl homo-serine lactones (AHLs) (1) and Pseudomonas quinoline signaling molecules (2) present in Gram-negative species, short peptide signals present in Gram-positive species, and autoinducer-2 (3) molecules found in both species (Figure 2). These help to control population density, swarming motility, virulence and biofilm formation [118][119][120]. The autoinducers initiate the formation of virulence factors that aid invasion and persistence in a vulnerable host.…”

Section: Interfering With Quorum-sensingmentioning

confidence: 99%

Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance

et al. 2022

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A biofilm is a community of stable microorganisms encapsulated in an extracellular matrix produced by themselves. Many types of microorganisms that are found on living hosts or in the environment can form biofilms. These include pathogenic bacteria that can serve as a reservoir for persistent infections, and are culpable for leading to a broad spectrum of chronic illnesses and emergence of antibiotic resistance making them difficult to be treated. The absence of biofilm-targeting antibiotics in the drug discovery pipeline indicates an unmet opportunity for designing new biofilm inhibitors as antimicrobial agents using various strategies and targeting distinct stages of biofilm formation. The strategies available to control biofilm formation include targeting the enzymes and proteins specific to the microorganism and those involved in the adhesion pathways leading to formation of resistant biofilms. This review primarily focuses on the recent strategies and advances responsible for identifying a myriad of antibiofilm agents and their mechanism of biofilm inhibition, including extracellular polymeric substance synthesis inhibitors, adhesion inhibitors, quorum sensing inhibitors, efflux pump inhibitors, and cyclic diguanylate inhibitors. Furthermore, we present the structure–activity relationships (SAR) of these agents, including recently discovered biofilm inhibitors, nature-derived bioactive scaffolds, synthetic small molecules, antimicrobial peptides, bioactive compounds isolated from fungi, non-proteinogenic amino acids and antibiotics. We hope to fuel interest and focus research efforts on the development of agents targeting the uniquely complex, physical and chemical heterogeneous biofilms through a multipronged approach and combinatorial therapeutics for a more effective control and management of biofilms across diseases.

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“…It has been reported that any mechanism with the capability of inhibiting any one of the key processes in the QS signals, named quorum quenching (QQ) can be potentially used for QQ sensing and preventing microbial infections. Given that research in QS inhibitors and QQ has been progressing so rapidly in recent years, the introduction of new mechanisms of QQ is inevitable [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Quorum quenching of Streptococcus mutans via the nano-quercetin-based antimicrobial photodynamic therapy as a potential target for cariogenic biofilm

et al. 2022

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Background Quorum sensing (QS) system can regulate the expression of virulence factors and biofilm formation in Streptococcus mutans. Antimicrobial photodynamic therapy (aPDT) inhibits quorum quenching (QQ), and can be used to prevent microbial biofilm. We thereby aimed to evaluate the anti-biofilm potency and anti-metabolic activity of nano-quercetin (N-QCT)-mediated aPDT against S. mutans. Also, in silico evaluation of the inhibitory effect of N-QCT on the competence-stimulating peptide (CSP) of S. mutans was performed to elucidate the impact of aPDT on various QS-regulated genes. Methods Cytotoxicity and intracellular reactive oxygen species (ROS) generation were assessed following synthesis and confirmation of N-QCT. Subsequently, the minimum biofilm inhibitory concentration (MBIC) of N-QCT against S. mutans and anti-biofilm effects of aPDT were assessed using colorimetric assay and plate counting. Molecular modeling and docking analysis were performed to confirm the connection of QCT to CSP. The metabolic activity of S. mutans and the expression level of various genes involved in QS were evaluated by flow cytometry and reverse transcription quantitative real-time PCR, respectively. Results Successful synthesis of non-toxic N-QCT was confirmed through several characterization tests. The MBIC value of N-QCT against S. mutans was 128 μg/mL. Similar to the crystal violet staining, the results log10 CFU/mL showed a significant degradation of preformed biofilms in the group treated with aPDT compared to the control group (P < 0.05). Following aPDT, metabolic activity of S. mutans also decreased by 85.7% (1/2 × MBIC of N-QCT) and 77.3% (1/4 × MBIC of N-QCT), as compared to the control values (P < 0.05). In silico analysis showed that the QCT molecule was located in the site formed by polypeptide helices of CSP. The relative expression levels of the virulence genes were significantly decreased in the presence of N-QCT-mediated aPDT (P < 0.05). Conclusions The combination of N-QCT with blue laser as a QQ-strategy leads to maximum ROS generation, disrupts the microbial biofilm of S. mutans, reduces metabolic activity, and downregulates the expression of genes involved in the QS pathway by targeting genes of the QS signaling system of S. mutans.

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<p>Quorum Quenching: A Potential Target for Antipseudomonal Therapy</p>

Cited by 53 publications

References 167 publications

Pyranoanthocyanins Interfering with the Quorum Sensing of Pseudomonas aeruginosa and Staphylococcus aureus

Pyranoanthocyanins Interfering with the Quorum Sensing of Pseudomonas aeruginosa and Staphylococcus aureus

Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance

Quorum quenching of Streptococcus mutans via the nano-quercetin-based antimicrobial photodynamic therapy as a potential target for cariogenic biofilm

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