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Coumarin reduces virulence and biofilm formation in Pseudomonas aeruginosa by affecting quorum sensing, type III secretion and C-di-GMP levels

Yunhui Zhang (UGent) , Andrea Sass (UGent) , Heleen Van Acker (UGent) , Jasper Wille (UGent) , Bruno Verhasselt (UGent) , Filip Van Nieuwerburgh (UGent) , Volkhard Kaever, Aurélie Crabbé (UGent) and Tom Coenye (UGent)
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Abstract
As one of the major pathogens in wound infections, Pseudomonas aeruginosa 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 P. aeruginosa infections. In the present study, we evaluated the effect of the plant-derived QS inhibitor coumarin on P. aeruginosa biofilms and virulence. Coumarin inhibited QS in the P. aeruginosa QSIS2 biosensor strain, reduced protease and pyocyanin production, and inhibited biofilm formation in microtiter plates in different P. aeruginosa strains. The effects of coumarin in inhibiting biofilm formation in an in vitro wound model and reducing P. aeruginosa virulence in the Lucilia sericata infection model were strain-dependent. Transcriptome analysis revealed that several key genes involved in the las, rhl, Pseudomonas quinolone signal (PQS), and integrated QS (IQS) systems were downregulated in coumarin-treated biofilms of P. aeruginosa 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 P. aeruginosa PAO1 and recent clinical P. aeruginosa 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 P. aeruginosa in wound infections.
Keywords
INHIBITORS, INFECTION, ANTIBIOTICS, RESISTANCE, STRAINS, SYSTEM, WOUNDS, PAO1, coumarin, Pseudomonas aeruginosa, biofilm, virulence, type III, secretion, c-di-GMP

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Chicago
Zhang, Yunhui, Andrea Sass, Heleen Van Acker, Jasper Wille, Bruno Verhasselt, Filip Van Nieuwerburgh, Volkhard Kaever, Aurélie Crabbé, and Tom Coenye. 2018. “Coumarin Reduces Virulence and Biofilm Formation in Pseudomonas Aeruginosa by Affecting Quorum Sensing, Type III Secretion and C-di-GMP Levels.” Frontiers in Microbiology 9.
APA
Zhang, Yunhui, Sass, A., Van Acker, H., Wille, J., Verhasselt, B., Van Nieuwerburgh, F., Kaever, V., et al. (2018). Coumarin reduces virulence and biofilm formation in Pseudomonas aeruginosa by affecting quorum sensing, type III secretion and C-di-GMP levels. FRONTIERS IN MICROBIOLOGY, 9.
Vancouver
1.
Zhang Y, Sass A, Van Acker H, Wille J, Verhasselt B, Van Nieuwerburgh F, et al. Coumarin reduces virulence and biofilm formation in Pseudomonas aeruginosa by affecting quorum sensing, type III secretion and C-di-GMP levels. FRONTIERS IN MICROBIOLOGY. 2018;9.
MLA
Zhang, Yunhui, Andrea Sass, Heleen Van Acker, et al. “Coumarin Reduces Virulence and Biofilm Formation in Pseudomonas Aeruginosa by Affecting Quorum Sensing, Type III Secretion and C-di-GMP Levels.” FRONTIERS IN MICROBIOLOGY 9 (2018): n. pag. Print.
@article{8578692,
  abstract     = {As one of the major pathogens in wound infections, Pseudomonas aeruginosa 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 P. aeruginosa infections. In the present study, we evaluated the effect of the plant-derived QS inhibitor coumarin on P. aeruginosa biofilms and virulence. Coumarin inhibited QS in the P. aeruginosa QSIS2 biosensor strain, reduced protease and pyocyanin production, and inhibited biofilm formation in microtiter plates in different P. aeruginosa strains. The effects of coumarin in inhibiting biofilm formation in an in vitro wound model and reducing P. aeruginosa virulence in the Lucilia sericata infection model were strain-dependent. Transcriptome analysis revealed that several key genes involved in the las, rhl, Pseudomonas quinolone signal (PQS), and integrated QS (IQS) systems were downregulated in coumarin-treated biofilms of P. aeruginosa 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 P. aeruginosa PAO1 and recent clinical P. aeruginosa 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 P. aeruginosa in wound infections.},
  articleno    = {1952},
  author       = {Zhang, Yunhui and Sass, Andrea and Van Acker, Heleen and Wille, Jasper and Verhasselt, Bruno and Van Nieuwerburgh, Filip and Kaever, Volkhard and Crabb{\'e}, Aur{\'e}lie and Coenye, Tom},
  issn         = {1664-302X},
  journal      = {FRONTIERS IN MICROBIOLOGY},
  language     = {eng},
  pages        = {10},
  title        = {Coumarin reduces virulence and biofilm formation in Pseudomonas aeruginosa by affecting quorum sensing, type III secretion and C-di-GMP levels},
  url          = {http://dx.doi.org/10.3389/fmicb.2018.01952},
  volume       = {9},
  year         = {2018},
}

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