• Journal of Microbiology and Biotechnology
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• v.20 no.12
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• pp.1624-1629
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• 2010

Bacterial cell-to-cell communication, termed quorum sensing (QS), leads to coordinated group behavior in a cell-density-dependent fashion and controls a variety of physiological processes including virulence gene expression. The repressor of the lsr operon, LsrR, is the only known regulator of LuxS/AI-2-mediated QS in Salmonella. Although lack of lsrR did not result in noticeable differences in Salmonella survival, the down-regulation of QS as a result of lsrR overexpression decreased Salmonella survival within macrophages. We found that impaired growth of Salmonella overexpressing lsrR within macrophages was due largely to its hypersensitivity to NADPH-dependent oxidative stress. This, in turn, was a result of decreased expression of genes involved in the oxidative stress response, such as sodA, sodCI, and sodCII, when lsrR was overexpressed. These results suggest that down-regulation of QS by excess LsrR can lower Salmonella virulence by hampering Salmonella evasion from oxidative killing within macrophages.

• International Journal of Oral Biology
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• v.46 no.3
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• pp.111-118
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• 2021

Periodontitis and periimplantitis are caused as a result of dental biofilm formation. This biofilm is composed of multiple species of pathogens. Therefore, controlling biofilm formation is critical for disease prevention. To inhibit biofilm formation, sugars can be used to interrupt lectin-involving interactions between bacteria or between bacteria and a host. In this study, we evaluated the effect of D-Arabinose on biofilm formation of putative periodontal pathogens as well as the quorum sensing activity and whole protein profiles of the pathogens. Crystal violet staining, confocal laser scanning microscopy, and scanning electron microscopy revealed that D-Arabinose inhibited biofilm formation of Porphyromonas gingivalis, Fusobacterium nucleatum, and Tannerella forsythia. D-Arabinose also significantly inhibited the activity of autoinducer 2 of F. nucleatum and the expression of representative bacterial virulence genes. Furthermore, D-Arabinose treatment altered the expression of some bacterial proteins. These results demonstrate that D-Arabinose can be used as an antibiofilm agent for the prevention of periodontal infections.

• Microbiology and Biotechnology Letters
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• v.50 no.1
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• pp.1-14
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• 2022

Bacteria communicate with each other through an intricate communication mechanism known as quorum sensing (QS). QS regulates different behavioral aspects in bacteria, such as biofilm formation, sporulation, virulence gene expression, antibiotic production, and bioluminescence. Several different chemical signals and signal detection systems play vital roles in promoting highly efficient intra- and interspecies communication. Gram-negative bacteria coordinate gene regulation through the production of acyl homoserine lactones (AHLs). Gram-positive bacteria do not code for AHL production, while some gram-negative bacteria have an incomplete AHL-QS system. Despite this fact, these microbes can detect AHLs owing to the presence of LuxR solo receptors. Various studies have reported the role of AHLs in interspecies signaling. Moreover, as bacteria live in a polymicrobial community, the production of extracellular compounds to compete for resources is imperative. Thus, AHL-mediated signaling and inhibition are considered to affect virulence in bacteria. In the current review, we focus on the synthesis and regulation mechanisms of AHLs and highlight their role in interspecies bacterial signaling. Exploring interspecies bacterial signaling will further help us understand host-pathogen interactions, thereby contributing to the development of therapeutic strategies intended to target chronic polymicrobial infections.

• Microbiology and Biotechnology Letters
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• v.39 no.1
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• pp.29-36
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• 2011

Pseudomonas aeruginosa is an opportunistic pathogen that causes various infections on urinary track, cornea, respiratory track, and burn wound site, and mainly relies on quorum sensing (QS) for its virulence. To control the infectivity of P. aeruginosa, we previously synthesized the structural analogues of a major QS signal, N-3-oxododecanoyl homoserine lactone (3OC12-HSL) to use as a QS inhibitor. Two of them (5b and 5f) had been confirmed to have an inhibitory effect on LasR, a major QS signal receptor of P. aeruginosa in the screening by the recombinant Escherichia coli reporter. To further evaluate these compounds, we tested their efficacy to control the QS and virulence of P. aeruginosa. Unlike the result from E. coli reporter, both 5b and 5f failed to affect the LasR activity in P. aeruginosa, but instead they selectively affected the activity of QscR, another 3OC12-HSL receptor of P. aeruginosa. Interestingly, their effect on QscR was complex and opposite to what we obtained with E. coli system. Both 5b and 5f enhanced the QscR activity at the low concentration range (< 10 ${\mu}m$), but high concentration of 5f (${\approx}$1 mM) strongly inhibited QscR. While 5b and 5f didn't affect the production of proteases, the key virulence factor, they significantly reduced the biofilm formation that is important in mediating chronic infections. Especially, 5f inhibited the initial attachment of P. aeruginosa, rather than the biofilm maturation. Based on our results, we suggest that 5f can be applied for an anti-biofilm agent without increasing virulence of P. aeruginosa.

• Journal of Microbiology and Biotechnology
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• v.30 no.4
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• pp.571-582
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• 2020

Quorum sensing (QS)-mediated infections cause severe diseases in human beings. The control of infectious diseases by inhibiting QS using antipathogenic drugs is a promising approach as antibiotics are proving inefficient in treating these diseases. Marine fungal (Pestalotiopsis sydowiana PPR) extract was found to possess effective antipathogenic characteristics. The minimum inhibitory concentration (MIC) of the fungal extract against test pathogen Pseudomonas aeruginosa PAO1 was 1,000 ㎍/ml. Sub-MIC concentrations (250 and 500 ㎍/ml) of fungal extract reduced QS-regulated virulence phenotypes such as the production of pyocyanin, chitinase, protease, elastase, and staphylolytic activity in P. aeruginosa PAO1 by 84.15%, 73.15%, 67.37%, 62.37%, and 33.65%, respectively. Moreover, it also reduced the production of exopolysaccharides (74.99%), rhamnolipids (68.01%), and alginate (54.98%), and inhibited the biofilm formation of the bacteria by 90.54%. In silico analysis revealed that the metabolite of P. sydowiana PPR binds to the bacterial QS receptor proteins (LasR and RhlR) similar to their respective natural signaling molecules. Cyclo(-Leu-Pro) (CLP) and 4-Hydroxyphenylacetamide (4-HPA) were identified as potent bioactive compounds among the metabolites of P. sydowiana PPR using in silico approaches. The MIC values of CLP and 4-HPA against P. aeruginosa PAO1 were determined as 250 and 125 ㎍/ml, respectively. All the antivirulence assays were conducted at sub-MIC concentrations of CLP (125 ㎍/ml) and 4-HPA (62.5 ㎍/ml), which resulted in marked reduction in all the investigated virulence factors. This was further supported by gene expression studies. The findings suggest that the metabolites of P. sydowiana PPR can be employed as promising QS inhibitors that target pathogenic bacteria.

• Fisheries and Aquatic Sciences
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• v.22 no.12
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• pp.30.1-30.11
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• 2019

Marine natural products isolated from the sponge Fascaplysinopsis cf reticulata, in French Polynesia, were investigated as an alternative to antibiotics to control pathogens in aquaculture. The overuse of antibiotics in aquaculture is largely considered to be an environmental pollution, because it supports the transfer of antibiotic resistance genes within the aquatic environment. One environmentally friendly alternative to antibiotics is the use of quorum sensing inhibitors (QSIs). Quorum sensing (QS) is a regulatory mechanism in bacteria which control virulence factors through the secretion of autoinducers (AIs), such as acyl-homoserine lactone (AHL) in gram-negative bacteria. Vibrio harveyi QS is controlled through three parallel pathways: HAI-1, AI-2, and CAI-1. Bioassay-guided purification of F. cf reticulata extract was conducted on two bacterial species, i.e., Tenacibaculum maritimum and V. harveyi for antibiotic and QS inhibition bioactivities. Toxicity bioassay of fractions was also evaluated on the freshwater fish Poecilia reticulata and the marine fish Acanthurus triostegus. Cyclohexanic and dichloromethane fractions of F. cf reticulata exhibited QS inhibition on V. harveyi and antibiotic bioactivities on V. harveyi and T. maritimum, respectively. Palauolide (1) and fascaplysin (2) were purified as major molecules from the cyclohexanic and dichloromethane fractions, respectively. Palauolide inhibited QS of V. harveyi through HAI-1 QS pathway at 50 ㎍ ml^-1 (26 μM), while fascaplysin affected the bacterial growth of V. harveyi (50 ㎍ ml^-1) and T. maritimum (0.25 ㎍). The toxicity of fascaplysin-enriched fraction (FEF) was evaluated and exhibited a toxic effect against fish at 50 ㎍ ml^-1. This study demonstrated for the first time the QSI potential of palauolide (1). Future research may assess the toxicity of both the cyclohexanic fraction of the sponge and palauolide (1) on fish, to confirm their potential as alternative to antibiotics in fish farming.

• Korean Journal of Microbiology
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• v.44 no.2
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• pp.85-92
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• 2008

Pseudomonas aeruginosa is an opportunistic human pathogen, causing a wide variety of infections including cystic fibrosis, microbial keratitis, and burn wound infections. The cell-to-cell signaling mechanism known as quorum sensing (QS) plays a key role in these infections and the QS systems of P. aeruginosa have been most intensively studied. While many literatures that introduce the QS systems of P. aeruginosa have mostly focused on two major acyl-homo serine lactone (acyl-HSL) QS signals, N-3-oxododecanoyl homoserine lactone (3OC12) and N-butanoyl homoserine lactone (C4), several new signal molecules have been discovered and suggested for their significant roles in signaling and virulence of P. aeruginosa. One of them is PQS (Pseudomonas quinolone signal; 2-heptyl-3-hydroxy-4-quinolone), which is now considered as a well-characterized major signal meolecule of P. aeruginosa. In addition, recent researches have also suggested some more putative signal molecules of P. aeruginosa, which are diketopiperazines (DKPs) and pyocyanin. DKPs are cyclic dipeptides and structurally diverse depending on what amino acids are involved in composition. Some DKPs from the culture supernatant of P. aeruginosa are suggested as new diffusible signal molecules, based on their ability to activate Vibrio fischeri LuxR biosensors that are previously considered specific for acyl-HSLs. Pyocyanin (1-hydroxy-5-methyl-phenazine), one of phenazine derivatives produced by P. aeruginosa is a characteristic blue-green pigment and redox-active compound. This has been recently suggested as a terminal signaling factor to upregulate some QS-controlled genes during stationary phase under the mediation of a transcription factor, SoxR. Here, details about these newly emerging signaling molecules of P. aeruginosa are discussed.

• Microbiology and Biotechnology Letters
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• v.43 no.4
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• pp.357-366
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• 2015

Quorum sensing (QS) is involved in the process of cell-to-cell communication and as a gene regulatory mechanism, which has been implicated in bacterial pathogenicity. Bacteria use this QS system to control a variety of physiological processes. In this study, pomegranate (Punica granatum L.) peel extract (PPE) was first screened for its ability to inhibit QS in bio-reporter strains (Chromobacterium violaceum and C. violaceum CV026). Next, the ability of PPE to inhibit swimming motility and biofilm formation was examined in Y. enterocolitica. Additionally, changes in the expression of specific genes involved in the synthesis of the N-acylhomoserine lactones (AHLs; yenI and yenR) and in the flagellar regulon (fliA, fleB and flhDC) were evaluated by reverse transcription (RT)-PCR. The results show that PPE specifically inhibited and reduced QS-controlled violacein production by 78.5% in C. violaceum CV026, and decreased QS-associated biofilm formation and swimming motility in Y. enterocolitica without significantly affecting bacterial growth. These inhibitory effects were also associated with the down-regulation of gene expression involved in the synthesis of AHLs and in motility. Our results suggest that PPE could be a potential therapeutic agent to prevent enteropathogens in humans, as well as highlight the need to further investigate the in vivo properties of PPE for clinical applications.

• Journal of Microbiology and Biotechnology
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• v.29 no.4
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• pp.596-606
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• 2019

N-acyl-homoserine lactone quorum sensing (AHL-QS) has been shown to regulate many physiological behaviors in Serratia marcescens MG1. In the current study, the effects of AHL-QS on the biosynthesis of acid and neutral products by S. marcescens MG1 and its isogenic ${\Delta}swrI$ with or without supplementing exogenous N-hexanoyl-L-homoserine lactone ($C_6-HSL$) were systematically investigated. The results showed that swrI disruption resulted in rapid pH drops from 7.0 to 4.8, which could be restored to wild type by supplementing $C_6-HSL$. Furthermore, fermentation product analysis indicated that ${\Delta}swrI$ could lead to obvious accumulation for acidogenesis products such as lactic acid and succinic acid, especially excess acetic acid (2.27 g/l) produced at the early stage of fermentation, whereas solventogenesis products by ${\Delta}swrI$ appeared to noticeably decrease by an approximate 30% for acetoin during 32-48 h and by an approximate 20% for 2,3-butanediol during 24-40 h, when compared to those by wild type. Interestingly, the excess acetic acid produced could be removed in an AHL-QS-independent manner. Subsequently, quantitative real-time PCR was used to determine the mRNA expression levels of genes responsible for acidogenesis and solventogenesis and showed consistent results with those of product synthesis. Finally, by close examination of promoter regions of the analyzed genes, four putative luxI box-like motifs were found upstream of genes encoding acetyl-CoA synthase, lactate dehydrogenase, ${\alpha}$-acetolactate decarboxylase, and Lys-like regulator. The information from this study provides a novel insight into the roles played by AHL-QS in switching from acidogenesis to solventogenesis in S. marcescens MG1.

• Journal of Life Science
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• v.31 no.1
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• pp.100-108
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• 2021

In the oral cavity, there are hundreds of microbial species that exist as planktonic cells or are incorporated into biofilms. The accumulation and proliferation of pathogenic bacteria in the oral biofilm can lead to caries and periodontitis, which are typical oral diseases. The oral bacteria in the biofilm not only can resist environmental stress inside the oral cavity, but also have a 1,000 times higher resistance to antibiotics than planktonic cells by genes exchange through the interaction between cells in the oral biofilm. Therefore, if the formation of oral biofilm is suppressed or removed, oral diseases caused by bacterial infection can be more effectively prevented or treated. In particular, since oral biofilms have the characteristic of forming a biofilm by gathering several bacteria, quorum sensing, a signaling system between cells, can be a target for controlling the oral biofilm. In addition, a method of inhibiting biofilm formation by using arginine, an alkali-producing substrate of oral bacteria, is used to convert the distribution of oral microorganisms into an environment similar to that of healthy teeth or inhibit the secretion of glucosyltransferase by S. mutans to inhibit the formation of non-soluble glucans. It can be a target to control oral biofilm. This method of inhibiting or removing the oral biofilm formation rather than inducing the death of pathogenic bacteria in the oral cavity will be a new strategy that can selectively prevent or therapeutic avenues for oral diseases including dental caries.