AUTHOR=Zhang Yunhui , Sass Andrea , Van Acker Heleen , Wille Jasper , Verhasselt Bruno , Van Nieuwerburgh Filip , Kaever Volkhard , Crabbé Aurélie , Coenye Tom 

TITLE=Coumarin Reduces Virulence and Biofilm Formation in Pseudomonas aeruginosa by Affecting Quorum Sensing, Type III Secretion and C-di-GMP Levels

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.01952

DOI=10.3389/fmicb.2018.01952

ISSN=1664-302X

ABSTRACT=<p>As one of the major pathogens in wound infections, <italic>Pseudomonas aeruginosa</italic> produces several virulence factors and forms biofilms; these processes are under the regulation of various quorum sensing (QS) systems. Therefore, QS has been regarded as a promising target to treat <italic>P. aeruginosa</italic> infections. In the present study, we evaluated the effect of the plant-derived QS inhibitor coumarin on <italic>P. aeruginosa</italic> biofilms and virulence. Coumarin inhibited QS in the <italic>P. aeruginosa</italic> QSIS2 biosensor strain, reduced protease and pyocyanin production, and inhibited biofilm formation in microtiter plates in different <italic>P. aeruginosa</italic> strains. The effects of coumarin in inhibiting biofilm formation in an <italic>in vitro</italic> wound model and reducing <italic>P. aeruginosa</italic> virulence in the <italic>Lucilia sericata</italic> infection model were strain-dependent. Transcriptome analysis revealed that several key genes involved in the <italic>las, rhl, Pseudomonas</italic> quinolone signal (PQS), and integrated QS (IQS) systems were downregulated in coumarin-treated biofilms of <italic>P. aeruginosa</italic> PAO1. Coumarin also changed the expression of genes related to type III secretion and cyclic diguanylate (c-di-GMP) metabolism. The cellular c-di-GMP level of <italic>P. aeruginosa</italic> PAO1 and recent clinical <italic>P. aeruginosa</italic> strains was significantly reduced by coumarin. These results provide new evidence for the possible application of coumarin as an anti-biofilm and anti-virulence agent against <italic>P. aeruginosa</italic> in wound infections.</p>