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|Title:||Comparative systems biology analysis to study the mode of action of the isothiocyanate compound iberin on pseudomonas aeruginosa||Authors:||Givskov, Michael
Nielsen, Thomas E.
Tan, Sean Yang-Yi
Chua, Song Lin
Vejborg, Rebecca Munk
Jakobsen, Tim Holm
Chew, Su Chuen
|Keywords:||DRNTU::Science::Biological sciences::Microbiology||Issue Date:||2014||Source:||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.||Series/Report no.:||Antimicrobial agents and chemotherapy||Abstract:||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.||URI:||https://hdl.handle.net/10356/100182
|DOI:||10.1128/AAC.02620-13||Rights:||© 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.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
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