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        Indole and 7-benzyloxyindole attenuate the virulence of Staphylococcus aureus

        Lee, Jin-Hyung,Cho, Hyun Seob,Kim, Younghoon,Kim, Jung-Ae,Banskota, Suhrid,Cho, Moo Hwan,Lee, Jintae Springer-Verlag 2013 Applied microbiology and biotechnology Vol.97 No.10

        <P>Human pathogens can readily develop drug resistance due to the long-term use of antibiotics that mostly inhibit bacterial growth. Unlike antibiotics, antivirulence compounds diminish bacterial virulence without affecting cell viability and thus, may not lead to drug resistance. Staphylococcus aureus is a major agent of nosocomial infections and produces diverse virulence factors, such as the yellow carotenoid staphyloxanthin, which promotes resistance to reactive oxygen species (ROS) and the host immune system. To identify novel antivirulence compounds, bacterial signal indole present in animal gut and diverse indole derivatives were investigated with respect to reducing staphyloxanthin production and the hemolytic activity of S. aureus. Treatment with indole or its derivative 7-benzyloxyindole (7BOI) caused S. aureus to become colorless and inhibited its hemolytic ability without affecting bacterial growth. As a result, S. aureus was more easily killed by hydrogen peroxide (H2O2) and by human whole blood in the presence of indole or 7BOI. In addition, 7BOI attenuated S. aureus virulence in an in vivo model of nematode Caenorhabditis elegans, which is readily infected and killed by S. aureus. Transcriptional analyses showed that both indole and 7BOI repressed the expressions of several virulence genes such as α-hemolysin gene hla, enterotoxin seb, and the protease genes splA and sspA and modulated the expressions of the important regulatory genes agrA and sarA. These findings show that indole derivatives are potential candidates for use in antivirulence strategies against persistent S. aureus infection.</P>

      • Fully integrated lab-on-a-disc for simultaneous analysis of biochemistry and immunoassay from whole blood

        Lee, Beom Seok,Lee, Yang Ui,Kim, Han-Sang,Kim, Tae-Hyeong,Park, Jiwoon,Lee, Jeong-Gun,Kim, Jintae,Kim, Hanshin,Lee, Wee Gyo,Cho, Yoon-Kyoung Royal Society of Chemistry 2011 Lab on a chip Vol.11 No.1

        <P>We report a fully integrated device that can perform both multiple biochemical analysis and sandwich type immunoassay simultaneously on a disc. The whole blood is applied directly to the disposable “lab-on-a-disc” containing different kinds of freeze-dried reagents for the blood chemistry analysis as well as reagents required for the immunoassay. The concentrations of different kinds of analytes are reported within 22 min by simply inserting a disc to a portable device. Using the innovative laser irradiated ferrowax microvalves together with the centrifugal microfluidics, the total process of plasma separation, metering, mixing, incubation, washing, and detection is fully automated. The analyzer is equipped with an optical detection module to measure absorbances at 10 different wavelengths to accommodate the various kinds of reaction protocols. Compared to the conventional blood analysis done in clinical laboratories, it is advantageous for point-of-care applications because it requires a smaller amount of blood (350 μL <I>vs.</I> 3 mL), takes less time (22 min <I>vs.</I> several days), does not require specially trained operators or expensive instruments to run biochemical analysis and immunoassay separately.</P> <P>Graphic Abstract</P><P>We report a fully integrated lab-on-a-disc system for simultaneous analysis of clinical chemistry and enzyme-linked immuno-sorbent assay (ELISA) from whole blood. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c0lc00205d'> </P>

      • Roles of Indole as an Interspecies and Interkingdom Signaling Molecule

        Lee, Jin-Hyung,Wood, Thomas K.,Lee, Jintae Elsevier 2015 Trends in microbiology Vol.23 No.11

        <P>A number of bacteria, and some plants, produce large quantities of indole, which is widespread in animal intestinal tracts and in the rhizosphere. Indole, as an interspecies and interkingdom signaling molecule, plays important roles in bacterial pathogenesis and eukaryotic immunity. Furthermore, indole and its derivatives are viewed as potential antivirulence compounds against antibiotic-resistant pathogens because of their ability to inhibit quorum sensing and virulence factor production. Indole modulates oxidative stress, intestinal inflammation, and hormone secretion in animals, and it controls plant defense systems and growth. Insects and nematodes can recognize indole, which controls some of their behavior. This review presents current knowledge regarding indole and its derivatives, their biotechnological applications and their role in prokaryotic and eukaryotic systems.</P> <P><B>Trends</B></P> <P>A variety of bacteria, and some plants, produce large quantities of indole, and thus, indole and its derivatives are widespread in prokaryotic and eukaryotic communities. Recently, indole was shown to be an intercellular, interspecies, and interkingdom signaling molecule.</P> <P>Indole and its derivatives can suppress the bacterial pathogenesis of several antibiotic-resistant pathogens by inhibiting quorum sensing and virulence factor production.</P> <P>Insects sense indole, which controls their behavior. Furthermore, indole controls plant defense systems and growth, and modulates oxidative stress, intestinal inflammation, and hormone secretion in animals. Emerging data suggest that indoles may influence human diseases, such as inflammatory, neurological, and metabolic diseases.</P>

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        Antimicrobial and antibiofilm activities of prenylated flavanones from <i>Macaranga tanarius</i>

        Lee, Jin-Hyung,Kim, Yong-Guy,Khadke, Sagar Kiran,Yamano, Aki,Woo, Je-Tae,Lee, Jintae Urban und Fischer Verlag 2019 Phytomedicine Vol.63 No.-

        <P><B>Abstract</B></P> <P><B>Background</B></P> <P>The emergence of antibiotic resistant microorganisms presents a worldwide problem that requires novel antibiotic and non-antibiotic strategies, and biofilm formation is a mechanism of drug resistance utilized by diverse microorganisms. The majority of microorganisms live in biofilms that help their survival against starvation, antimicrobial agents, and immunological defense systems. Therefore, it is important novel compounds be identified that inhibit biofilm formation and cell survival without drug resistance.</P> <P><B>Study design</B></P> <P>In this study, the antimicrobial and antibiofilm activities of five prenylated flavanones (Okinawan propolins) isolated from fruits of <I>Macaranga tanarius</I> (L.) were investigated against 14 microorganisms including 10 pathogens.</P> <P><B>Results</B></P> <P>Of these five propolins, propolin D at 5–10 µg/ml significantly inhibited biofilm formation by three <I>Staphylococcus aureus</I> strains, a <I>Staphylococcus epidermidis</I> strain, and a <I>Candida albicans</I> with MICs from 10 to 50 µg/ml, and in <I>C. albicans</I>, propolin D was found to inhibit biofilm formation by reducing cell aggregation and downregulated the expressions of hypha/biofilm-related genes including <I>ECE1</I> and <I>HWP1</I>. Interestingly, at sub-MIC concentrations (10–50 µg/ml), propolin D significantly inhibited biofilm formation by enterohemorrhagic <I>E. coli</I> O157:H7, uropathogenic <I>E. coli</I> O6:H1, and <I>Acinetobacter baumannii</I> without affecting planktonic cell growth, but did not inhibit biofilm formation by a commensal <I>E. coli</I> K-12 strain, three probiotic <I>Lactobacillus plantarum</I> strains, or two <I>Pseudomonas aeruginosa</I> strains. And, propolin D reduced fimbriae production by <I>E. coli</I> O157:H7 and repressed gene expression of curli fimbriae genes (<I>csgA</I> and <I>csgB</I>). Also, propolin D was minimally toxic in a <I>Caenorhabditis elegans</I> nematode model.</P> <P><B>Conclusion</B></P> <P>These findings show that prenylated flavanones, especially propolin D from <I>Macaranga tanarius</I> (Okinawan propolis), should be considered potential candidates for the development of non-toxic antibacterial and antifungal agents against persistent microorganisms.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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        3‐Indolylacetonitrile Decreases <i>Escherichia coli</i> O157:H7 Biofilm Formation and <i>Pseudomonas aeruginosa</i> Virulence

        Lee, Jin‐,Hyung,Cho, Moo Hwan,Lee, Jintae Blackwell Publishing Ltd 2011 ENVIRONMENTAL MICROBIOLOGY Vol.13 No.1

        <P><B>Summary</B></P><P>Intercellular signal indole and its derivative hydroxyindoles inhibit <I>Escherichia coli</I> biofilm and diminish <I>Pseudomonas aeruginosa</I> virulence. However, indole and bacterial indole derivatives are unstable in the microbial community because they are quickly degraded by diverse bacterial oxygenases. Hence, this work sought to identify novel, non‐toxic, stable and potent indole derivatives from plant sources for inhibiting the biofilm formation of <I>E. coli</I> O157:H7 and <I>P. aeruginosa</I>. Here, plant auxin 3‐indolylacetonitrile (IAN) was found to inhibit the biofilm formation of both <I>E. coli</I> O157:H7 and <I>P. aeruginosa</I> without affecting its growth. IAN more effectively inhibited biofilms than indole for the two pathogenic bacteria. Additionally, IAN decreased the production of virulence factors including 2‐heptyl‐3‐hydroxy‐4(1<I>H</I>)‐quinolone (PQS), pyocyanin and pyoverdine in <I>P. aeruginosa</I>. DNA microarray analysis indicated that IAN repressed genes involved in curli formation and glycerol metabolism, whereas IAN induced indole‐related genes and prophage genes in <I>E. coli</I> O157:H7. It appeared that IAN inhibited the biofilm formation of <I>E. coli</I> by reducing curli formation and inducing indole production. Also, corroborating phenotypic results of <I>P. aeruginosa</I>, whole‐transcriptomic data showed that IAN repressed virulence‐related genes and motility‐related genes, while IAN induced several small molecule transport genes. Furthermore, unlike bacterial indole derivatives, plant‐originated IAN was stable in the presence of either <I>E. coli</I> or <I>P. aeruginosa</I>. Additionally, indole‐3‐carboxyaldehyde was another natural biofilm inhibitor for both <I>E. coli</I> and <I>P. aeruginosa</I>.</P>

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        Antibiofilm activities of norharmane and its derivatives against <i>Escherichia coli</i> O157:H7 and other bacteria

        Lee, Jin-Hyung,Kim, Yong-Guy,Shim, Sang Hee,Lee, Jintae Elsevier 2017 Phytomedicine Vol.36 No.-

        <P>Conclusion: These findings strongly suggest that harmaline and norharmane could have potential use in antibiofilm strategy against persistent bacterial infections.</P>

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