Comparative systems biology analysis to study the mode of action of the isothiocyanate compound iberin on pseudomonas aeruginosa

Food is now recognized as a natural resource of novel antimicrobial agents, including those that target the virulence mechanisms of bacterial pathogens. Iberin, an isothiocyanate compound from horseradish, was recently identified as a quorum-sensing inhibitor (QSI) of the bacterial pathogen Pseudomo...

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Main Authors: Givskov, Michael, Nielsen, Thomas E., Tolker-Nielsen, Tim, Tan, Sean Yang-Yi, Liu, Yang, Chua, Song Lin, Vejborg, Rebecca Munk, Jakobsen, Tim Holm, Chew, Su Chuen, Li, Yingying, Yang, Liang
Other Authors: Interdisciplinary Graduate School (IGS)
Format: Article
Language:English
Published: 2015
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Online Access:https://hdl.handle.net/10356/100182
http://hdl.handle.net/10220/25683
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1001822022-02-16T16:31:07Z Comparative systems biology analysis to study the mode of action of the isothiocyanate compound iberin on pseudomonas aeruginosa Givskov, Michael Nielsen, Thomas E. Tolker-Nielsen, Tim Tan, Sean Yang-Yi Liu, Yang Chua, Song Lin Vejborg, Rebecca Munk Jakobsen, Tim Holm Chew, Su Chuen Li, Yingying Yang, Liang Interdisciplinary Graduate School (IGS) School of Biological Sciences Singapore Centre for Environmental Life Sciences Engineering DRNTU::Science::Biological sciences::Microbiology Food is now recognized as a natural resource of novel antimicrobial agents, including those that target the virulence mechanisms of bacterial pathogens. Iberin, an isothiocyanate compound from horseradish, was recently identified as a quorum-sensing inhibitor (QSI) of the bacterial pathogen Pseudomonas aeruginosa. In this study, we used a comparative systems biology approach to unravel the molecular mechanisms of the effects of iberin on QS and virulence factor expression of P. aeruginosa. Our study shows that the two systems biology methods used (i.e., RNA sequencing and proteomics) complement each other and provide a thorough overview of the impact of iberin on P. aeruginosa. RNA sequencing-based transcriptomics showed that iberin inhibits the expression of the GacA-dependent small regulatory RNAs RsmY and RsmZ; this was verified by using gfp-based transcriptional reporter fusions with the rsmY or rsmZ promoter regions. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics showed that iberin reduces the abundance of the LadS protein, an activator of GacS. Taken together, the findings suggest that the mode of QS inhibition in iberin is through downregulation of the Gac/Rsm QS network, which in turn leads to the repression of QS-regulated virulence factors, such as pyoverdine, chitinase, and protease IV. Lastly, as expected from the observed repression of small regulatory RNA synthesis, we also show that iberin effectively reduces biofilm formation. This suggests that small regulatory RNAs might serve as potential targets in the future development of therapies against pathogens that use QS for controlling virulence factor expression and assume the biofilm mode of growth in the process of causing disease. Published version 2015-05-26T08:58:33Z 2019-12-06T20:17:57Z 2015-05-26T08:58:33Z 2019-12-06T20:17:57Z 2014 2014 Journal Article Tan, S. Y.-Y., Liu, Y., Chua, S. L., Vejborg, R. M., Jakobsen, T. H., Chew, S. C., et al. (2014). Comparative systems biology analysis to study the mode of action of the isothiocyanate compound iberin on pseudomonas aeruginosa. Antimicrobial agents and chemotherapy, 58(11), 6648-6659. https://hdl.handle.net/10356/100182 http://hdl.handle.net/10220/25683 10.1128/AAC.02620-13 25155599 en Antimicrobial agents and chemotherapy © 2014 American Society for Microbiology. This paper was published in Antimicrobial Agents and Chemotherapy and is made available as an electronic reprint (preprint) with permission of American Society for Microbiology. The paper can be found at the following official DOI: [http://dx.doi.org/10.1128/AAC.02620-13]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences::Microbiology
spellingShingle DRNTU::Science::Biological sciences::Microbiology
Givskov, Michael
Nielsen, Thomas E.
Tolker-Nielsen, Tim
Tan, Sean Yang-Yi
Liu, Yang
Chua, Song Lin
Vejborg, Rebecca Munk
Jakobsen, Tim Holm
Chew, Su Chuen
Li, Yingying
Yang, Liang
Comparative systems biology analysis to study the mode of action of the isothiocyanate compound iberin on pseudomonas aeruginosa
description Food is now recognized as a natural resource of novel antimicrobial agents, including those that target the virulence mechanisms of bacterial pathogens. Iberin, an isothiocyanate compound from horseradish, was recently identified as a quorum-sensing inhibitor (QSI) of the bacterial pathogen Pseudomonas aeruginosa. In this study, we used a comparative systems biology approach to unravel the molecular mechanisms of the effects of iberin on QS and virulence factor expression of P. aeruginosa. Our study shows that the two systems biology methods used (i.e., RNA sequencing and proteomics) complement each other and provide a thorough overview of the impact of iberin on P. aeruginosa. RNA sequencing-based transcriptomics showed that iberin inhibits the expression of the GacA-dependent small regulatory RNAs RsmY and RsmZ; this was verified by using gfp-based transcriptional reporter fusions with the rsmY or rsmZ promoter regions. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics showed that iberin reduces the abundance of the LadS protein, an activator of GacS. Taken together, the findings suggest that the mode of QS inhibition in iberin is through downregulation of the Gac/Rsm QS network, which in turn leads to the repression of QS-regulated virulence factors, such as pyoverdine, chitinase, and protease IV. Lastly, as expected from the observed repression of small regulatory RNA synthesis, we also show that iberin effectively reduces biofilm formation. This suggests that small regulatory RNAs might serve as potential targets in the future development of therapies against pathogens that use QS for controlling virulence factor expression and assume the biofilm mode of growth in the process of causing disease.
author2 Interdisciplinary Graduate School (IGS)
author_facet Interdisciplinary Graduate School (IGS)
Givskov, Michael
Nielsen, Thomas E.
Tolker-Nielsen, Tim
Tan, Sean Yang-Yi
Liu, Yang
Chua, Song Lin
Vejborg, Rebecca Munk
Jakobsen, Tim Holm
Chew, Su Chuen
Li, Yingying
Yang, Liang
format Article
author Givskov, Michael
Nielsen, Thomas E.
Tolker-Nielsen, Tim
Tan, Sean Yang-Yi
Liu, Yang
Chua, Song Lin
Vejborg, Rebecca Munk
Jakobsen, Tim Holm
Chew, Su Chuen
Li, Yingying
Yang, Liang
author_sort Givskov, Michael
title Comparative systems biology analysis to study the mode of action of the isothiocyanate compound iberin on pseudomonas aeruginosa
title_short Comparative systems biology analysis to study the mode of action of the isothiocyanate compound iberin on pseudomonas aeruginosa
title_full Comparative systems biology analysis to study the mode of action of the isothiocyanate compound iberin on pseudomonas aeruginosa
title_fullStr Comparative systems biology analysis to study the mode of action of the isothiocyanate compound iberin on pseudomonas aeruginosa
title_full_unstemmed Comparative systems biology analysis to study the mode of action of the isothiocyanate compound iberin on pseudomonas aeruginosa
title_sort comparative systems biology analysis to study the mode of action of the isothiocyanate compound iberin on pseudomonas aeruginosa
publishDate 2015
url https://hdl.handle.net/10356/100182
http://hdl.handle.net/10220/25683
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