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Lee, Jin-Hyung,Kim, Yong-Guy,Kim, Chang-Jin,Lee, Jae-Chan,Cho, Moo Hwan,Lee, Jintae Springer-Verlag 2012 Applied microbiology and biotechnology Vol.96 No.4
<P>Pathogenic biofilms have been associated with persistent infections due to their high resistance to antimicrobial agents. To identify nontoxic biofilm inhibitors for enterohemorrhagic Escherichia coli O157:H7, the spent media of a 4,104 Actinomycetes library was screened. The culture spent medium (1%, v/v) of plant pathogen Rhodococcus sp. BFI 332 markedly inhibited E. coli O157:H7 biofilm formation without affecting the growth of planktonic E. coli O157:H7 cells. Rhodococcus sp. BFI 332 produced significant amounts of indole-3-acetaldehyde and indole-3-acetic acid, and the former of which reduced E. coli O157:H7 biofilm formation. Global transcriptome analyses showed that indole-3-acetaldehyde most repressed two curli operons, csgBAC and csgDEFG, and induced tryptophanase (tnaAB) in E. coli O157:H7 biofilm cells. Electron microscopy showed that spent medium of Rhodococcus sp. BFI 332 and indole-3-acetaldehyde reduced curli production in E. coli O157:H7. The spent medium of Rhodococcus sp. BFI 332 also significantly reduced the biofilm formation of Staphylococcus aureus and Staphylococcus epidermidis. Overall, this study suggests that indole derivatives are present in the Actinomycetes strains and they can be used as biofilm inhibitors against pathogenic bacteria.</P>
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>
Lee, Jin-Hyung,Kim, Yong-Guy,Lee, Kayeon,Kim, Chang-Jin,Park, Dong-Jin,Ju, Yoonjung,Lee, Jae-Chan,Wood, Thomas K.,Lee, Jintae Informa UK (TaylorFrancis) 2016 BIOFOULING -CHUR- Vol.32 No.1
<P>Staphylococcus aureus is a versatile human pathogen that produces diverse virulence factors, and its biofilm cells are difficult to eradicate due to their inherent ability to tolerate antibiotics. The anti-biofilm activities of the spent media of 252 diverse endophytic microorganisms were investigated using three S. aureus strains. An attempt was made to identify anti-biofilm compounds in active spent media and to assess their anti-hemolytic activities and hydrophobicities in order to investigate action mechanisms. Unlike other antibiotics, actinomycin D (0.5 mu g ml(-1)) from Streptomyces parvulus significantly inhibited biofilm formation by all three S. aureus strains. Actinomycin D inhibited slime production in S. aureus and it inhibited hemolysis by S. aureus and caused S. aureus cells to become less hydrophobic, thus supporting its anti-biofilm effect. In addition, surface coatings containing actinomycin D prevented S. aureus biofilm formation on glass surfaces. Given these results, FDA-approved actinomycin D warrants further attention as a potential antivirulence agent against S. aureus infections.</P>
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>
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>
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>