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.
Highlights
The opportunistic pathogen Pseudomonas aeruginosa frequently causes diverse infections in immunocompromised patients (Lyczak et al, 2000; Obritsch et al, 2005; Gellatly and Hancock, 2013), and is involved in both acute and chronic wound infections associated with high morbidity and mortality
Coumarin reduced protease production in P. aeruginosa PAO1 and the five clinical strains, to varying degrees (p < 0.05) (Figure 2B). These results indicate that coumarin inhibits the production of quorum sensing (QS)-regulated virulence factors in different P. aeruginosa clinical strains
Coumarin was previously described as a QS inhibitors (QSIs) in P. aeruginosa (Gutiérrez-Barranquero et al, 2015) and this was confirmed in the present study
Summary
The opportunistic pathogen Pseudomonas aeruginosa frequently causes diverse infections in immunocompromised patients (Lyczak et al, 2000; Obritsch et al, 2005; Gellatly and Hancock, 2013), and is involved in both acute and chronic wound infections associated with high morbidity and mortality. Chronic wounds such as diabetic ulcers, venous ulcers, and pressure ulcers affect millions of patients worldwide and lead to high costs for the healthcare system (e.g., they represent an estimated cost of around 25 billion per year in the United States alone) (Sen et al, 2009). There is an urgent need to develop alternative strategies to combat biofilmrelated P. aeruginosa infections
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