• Microbiology and Biotechnology Letters
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• v.32 no.1
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• pp.1-10
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• 2004

Many bacteria monitor their population density and control the expression of specialized gene sets in response to bacterial cell density based on a mechanism referred to as quorum sensing. In all cases, quorum sensing involves the production and detection of extracellular signaling molecules, auto inducers, as which Gram-negative and Gram-positive bacteria use most prevalently acylated homoserine lactones and processed oligo-peptides, respectively. Through quorum-sensing communication circuits, bacteria regulate a diverse array of physiological functions, including virulence, symbiosis, competence, conjugation, antibiotic production, motility, sporulation, and biofilm formation. Many pathogens have evolved quorum-sensing mechanisms to mount population-density-dependent attacks to over-whelm the defense responses of plants, animals, and humans. Since these AHL-mediated signaling mechanisms are widespread and highly conserved in many pathogenic bacteria, the disruption of quorum-sensing system might be an attractive target for novel anti-infective therapy. To control AHL-mediated pathogenicity, several promising strategies to disrupt bacterial quorum sensing have been reported, and several chemicals and enzymes have been also investigated for years. These studies indicate that anti-quorum sensing strategies could be developed as possible alternatives of antibiotics.

• Journal of Pharmacopuncture
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• v.25 no.1
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• pp.37-45
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• 2022

Objectives: The quorum-sensing-inhibitory and anti-biofilm activities of the methanol extract of E. globulus leaves were determined against clinically isolated multidrug-resistant Pseudomonas aeruginosa. Methods: The preliminary anti-quorum-sensing (AQS) activity of eucalyptus was investigated against a biosensor strain Chromobacterium violaceum ATCC 12472 (CV12472) by using the agar well diffusion method. The effect of sub-minimum inhibitory concentrations (sub-MICs) of the methanol extract of eucalyptus on different quorum-sensing-regulated virulence factors, such as swarming motility, pyocyanin pigment, exopolysaccharide (EPS), and biofilm formation, against clinical isolates (CIs 2, 3, and 4) and reference PA01 of Pseudomonas aeruginosa were determined using the swarm diameter (mm)-measurement method, chloroform extraction method, phenol (5%)-sulphuric acid (concentrated) method, and the microtiter plate assay respectively, and the inhibition (%) in formation were calculated. Results: The preliminary AQS activity (violacein pigment inhibition) of eucalyptus was confirmed against Chromobacterium violaceum ATCC 12472 (CV12472). The eucalyptus extract also showed concentration-dependent inhibition (%) of swarming motility, pyocyanin pigment, EPS, and biofilm formation in different CIs and PA01 of P. aeruginosa. Conclusion: Our results revealed the effectiveness of the E. globulus extract for the regulation of quorum-sensing-dependent virulence factors and biofilm formation at a reduced dose (sub-MICs) and suggest that E. globulus may be a therapeutic agent for curing and controlling bacterial infection and thereby reducing the possibility of resistance development in pathogenic strains.

• Microbiology and Biotechnology Letters
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• v.40 no.2
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• pp.83-91
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• 2012

Quorum sensing (QS) is a cell-to-cell communication system, which is used by many bacteria to regulate diverse gene expression in response to changes in population density. Bacteria recognize the differences in cell density by sensing the concentration of signal molecules such as N-acyl-homoserine lactones (AHL) and autoinducer-2 (AI-2). In particular, QS plays a key role in biofilm formation, which is a specific bacterial group behavior. Biofilms are dense aggregates of packed microbial communities that grow on surfaces, and are embedded in a self-produced matrix of extracellular polymeric substances (EPS). QS regulates biofilm dispersal as well as the production of EPS. In some bacteria, biofilm formations are regulated by c-di-GMP-mediated signaling as well as QS, thus the two signaling systems are mutually connected. Biofilms are one of the major virulence factors in pathogenic bacteria. In addition, they cause numerous problems in industrial fields, such as the biofouling of pipes, tanks and membrane bioreactors (MBR). Therefore, the interference of QS, referred to as quorum quenching (QQ) has received a great deal of attention. To inhibit biofilm formation, several strategies to disrupt bacterial QS have been reported, and many enzymes which can degrade or modify the signal molecule AHL have been studied. QQ enzymes, such as AHL-lactonase, AHL-acylase, and oxidoreductases may offer great potential for the effective control of biofilm formation and membrane biofouling in the future. This review describes the process of bacterial QS, biofilm formation, and the close relationship between them. Finally, QQ enzymes and their applications for the reduction of biofouling are also discussed.

• Journal of Pharmacopuncture
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• v.26 no.4
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• pp.307-318
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• 2023

Objectives: Bacterial biofilm is regarded as a significant threat to the production of safe food and the arise of antibiotic-resistant bacteria. The objective of this investigation is to evaluate the quorum sensing inhibitory effect of Nepeta curviflora methanolic extract. Methods: The effectiveness of the leaves at sub-inhibitory concentrations of 2.5, 1.25, and 0.6 mg/mL on the virulence factors and biofilm formation of P. aeruginosa was evaluated. The effect of N. curviflora methanolic extract on the virulence factors of P. aeruginosa, including pyocyanin, rhamnolipid, protease, and chitinase, was evaluated. Other tests including the crystal violet assay, scanning electron microscopy (SEM), swarming motility, aggregation ability, hydrophobicity and exopolysaccharide production were conducted to assess the effect of the extract on the formation of biofilm. Insight into the mode of antiquorum sensing action was evaluated by examining the effect of the extract on the activity of N-Acyl homoserine lactone (AHL) and the expression of pslA and pelA genes. Results: The results showed a significant attenuation in the production of pyocyanin and rhamnolipid and in the activities of protease and chitinase enzymes at 2.5 and 1.25 mg/mL. In addition, N. curviflora methanolic extract significantly inhibited the formation of P. aeruginosa biofilm by decreasing aggregation, hydrophobicity, and swarming motility as well as the production of exopolysaccharide (EPS). A significant reduction in AHL secretion and pslA gene expression was observed, indicating that the extract inhibited quorum sensing by disrupting the quorum-sensing systems. The quorum-sensing inhibitory effect of N. curviflora extract appears to be attributed to the presence of kaempferol, quercetin, salicylic acid, rutin, and rosmarinic acid, as indicated by LCMS analysis. Conclusion: The results of the present study provide insight into the potential of developing anti-quorum sensing agents using the extract and the identified compounds to treat infections resulting from quorum sensing-mediated bacterial pathogenesis.

• Journal of Environmental Science International
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• v.30 no.5
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• pp.369-378
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• 2021

In this study, we investigated the effects of indole on biofilm formation inhibition in Pantoea agglomerans (P. agglomerans). In the biofilm growth assay, indole inhibited biofilm formation across all the growth time. Depending on biofilm growth stage, indole exhibited biofilm inhibition and anti-bacterial effects on planktonic cells. Through the analysis of the proportion rate between biofilm and Colony Forming Units (CFU) and inhibition rate of indole, we confirmed that depending on the biofilm stage of P. agglomerans, indole treatment timing was more important than the treatment duration. By comparing gene expression rates through rt-qPCR P.agglomerans affected by indole was found to significantly change quorum sensing (pagI/R) and indole transportation (bssS) gene expressions. Throughout all, indole exhibited both antimicrobial and anti-biofilm effects on P. agglomerans. In addition, we confirmed the anti-biofilm effects of indole on mature biofilm. In conclusion, indole as a signal molecule, can exhibit anti-biofilm effects through bacterial quorum sensing inhibition and indole affects. Therefore, indole can regulate biofilm bacteria especially gram-negative opportunistic pathogens.

• Membrane and Water Treatment
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• v.6 no.3
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• pp.189-203
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• 2015

Membrane biofouling impedes wide application of membrane bioreactor (MBR) for wastewater treatment. Recently, quorum sensing (QS) mechanisms are accounted for one of major mechanisms in biofouling of MBRs. In this study, vanillin was applied to investigate reduction of biofouling in MBRs. MBR sludge was analyzed to contain QS signal molecules by cross-feeding biosensor assay and HPLC. In addition, the inhibitory activity of vanillin against bacterial quorum sensing was verified using an indicator strain CV026. The vanillin doses greater than 125 mg/L to 100 mL of MBR sludge showed 25% reduction of biofilm formed on the membrane surfaces. Two MBRs, i.e., a typical MBR as a control and an MBR with vanillin, were operated. The TMP increases of the control MBR were more rapid compared to those of the MBR with the vanillin dose of 250 mg/L. The treatment efficiencies of the two MBRs on organic removal and MLSS were maintained relatively constant. Extracellular polymeric substance concentrations measured at the end of the MBR operation were 173 mg/g biocake for the control MBR and 119 mg/g biocake for the MBR with vanillin. Vanillin shows great potential as an anti-biofouling agent for MBRs without any interference on microbial activity for wastewater treatment.

• Natural Product Sciences
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• v.25 no.2
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• pp.172-180
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• 2019

Infections with Pseudomonas aeruginosa are difficult to treat not only because it is often associated with multidrug-resistant infections but also it is able to form biofilm. The aim of this study was to evaluate the antibiofilm and anti-Quorum Sensing (QS) activities of Thymbra capitata essential oils (EOs) against Beta Lactamase (BL) producing P. aeruginosa and the reference strain P. aeruginosa 10145. GC/MS analysis showed that thymol (23.25%) is the most dominant compound in T. capitata EOs. The MICs of T. capitata EOs against P. aeruginosa (BL) and P. aeruginosa 10145 were 1.11%. At sub MIC (0.041, 0.014 and 0.0046%), the EOs of T. capitata remarkably inhibited the biofilm formation of both strains tested and complete inhibition of the biofilm formation was reported at 0.041%. The EOs of T. capitata were found to inhibit the swarming motility, aggregation ability and hydrophobic ability of P. aeruginosa (BL) and P. aeruginosa 10145. Interestingly, the EOs of T. capitata reduce the production of three secreted virulence factors that regulated by QS system including pyocyanin, rhamnolipids and LasA protease. The potent antibiofilm and anti-QS activities of T. capitata EOs can propose it as a new antibacterial agent to control pseudomonas infections.

• Journal of Life Science
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• v.26 no.12
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• pp.1487-1497
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• 2016

Bacterial cell to cell communication strategies called quorum sensing (QS) using small diffusible signaling molecules (auto-inducers) govern the expression of various genes dependent on their population density manner. As a consequence of synthesis and response to the signaling molecules, individual planktonic cells synchronized group behaviors to control a diverse array of phenotypes such as maturation of biofilm, production of extra-polymeric substances (EPS), virulence, bioluminescence and antibiotic production. Many studies indicated that biofilm formations are associated with QS signaling molecules such as acyl-homoserine lactones (AHLs) mainly used by several Gram negative bacteria. The biofilm maturation causes undesirable biomass accumulation in various surface environments anywhere water is present called biofouling, which results in serious eco-technological problems. Numerous molecules that interfere the bacterial QS called quorum quenching (QQ), have been discovered from various microorganisms, and their functions and mechanisms associated with QS have also been elucidated. To resolve biofouling problems related to various industries, the novel approach based on QS interference has been emerged attenuating multi-drug resisting bacteria appearance and environmental toxicities, which may provide potential advantages over the conventional anti-biofouling approaches. Therefore this paper presents recent information related to bacterial quorum sensing system, quorum quenching enzymes that can control the QS signaling, and lastly discuss the anti-biofouling approaches using the quorum quenching.

• Food Science of Animal Resources
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• v.40 no.6
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• pp.1001-1013
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• 2020

The formation of biofilms on the enamel surface of teeth by Streptococcus mutans is an important step in dental plaque formation, demineralization, and early caries because the biofilm is where other bacteria involved in dental caries attach, grow, and proliferate. The objectives of this study were to determine the effect of phosvitin (PSV) on the biofilm formation, exopolysaccharides (EPS) production, adherence activity of S. mutans, and the expression of genes related to the compounds essential for biofilm formation (quorum-sensing inducers and components of biofilm matrix) by S. mutans. PSV significantly reduced the biofilm-forming activity of S. mutans and increased the degradation of preformed biofilms by S. mutans. PSV inhibited the adherence activity of S. mutans by 31.9%-33.6%, and the production of EPS by 62%-65% depending upon the strains and the amount of PSV added. The expressions of genes regulating the production of EPS and the quorum-sensing-inducers (gtfA, gtfD, ftf, relA, vicR, brpA, and comDE) in all S. mutans strains were down-regulated by PSV, but gtfB was down-regulated only in S. mutans KCTC 5316. Therefore, the anti-biofilm-forming activity of PSV was accomplished through the inhibition of biofilm formation, adherence activity, and the production of quorum-sensing inducers and EPS by S. mutans.

• Journal of Microbiology and Biotechnology
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• v.32 no.2
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• pp.220-227
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• 2022

The spread of antibiotic-resistant strains of Staphylococcus aureus, a gram-positive opportunistic pathogen, has increased due to the frequent use of antibiotics. Inhibition of the quorum-sensing systems of biofilm-producing strains using plant extracts represents an efficient approach for controlling infections. Torilis japonica is a medicinal herb showing various bioactivities; however, no studies have reported the anti-biofilm effects of T. japonica extracts against drug-resistant S. aureus. In this study, we evaluated the inhibitory effects of T. japonica ethanol extract (TJE) on biofilm production in methicillin-sensitive S. aureus (MSSA) KCTC 1927, methicillin-resistant S. aureus (MRSA) KCCM 40510, and MRSA KCCM 40511. Biofilm assays showed that TJE could inhibit biofilm formation in all strains. Furthermore, the hemolysis of sheep blood was found to be reduced when the strains were treated with TJE. The mRNA expression of agrA, sarA, icaA, hla, and RNAIII was evaluated using reverse transcription-polymerase chain reaction to determine the effect of TJE on the regulation of genes encoding quorum sensing-related virulence factors in MSSA and MRSA. The expression of hla reduced in a concentration-dependent manner upon treatment with TJE. Moreover, the expression levels of other genes were significantly reduced compared to those in the control group. In conclusion, TJE can suppress biofilm formation and virulence factor-related gene expression in MSSA and MRSA strains. The extract may therefore be used to develop treatments for infections caused by antibiotic-resistant S. aureus.