Comparative systems biology analysis and mode of action of the isothiocyanate compound iberin on Pseudomonas aeruginosa
Reference: Antimicrobial Agents and Chemotherapy (2014) 58(11): 6648-6659

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. Here, we used a comparative systems biology approach to unravel the molecular mechanisms of iberin's effects on QS and virulence factor expression of P. aeruginosa. Our study shows that both of the 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. iTRAQ proteomics showed that iberin reduces the abundance of the LadS protein, an activator of GacS. Taken together, the findings suggest that iberin's mode of QS inhibition is through down-regulation of the Gac/Rsm QS network which in turn leads to 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 for 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 By
Tan S.Y., Liu Y., Chua S. L., Vejborg R.M., Jakobsen T.H., Chew S.C., Li Y., Nielsen T.E., Tolker-Nielsen T., Yang L., Givskov M.