Investigating the effect of the probiotic Lactobacillus plantarum and the prebiotic fructooligosaccharides on Pseudomonas aeruginosa metabolome, virulence factors and biofilm formation as potential quorum sensing inhibitors

Pseudomonas aeruginosa (P. aeruginosa) uses quorum sensing signaling (QS) molecules to control the expression of virulence factors and biofilm formation. In this study, the effects of the probiotic's (Lactobacillus plantarum (L. plantarum)) lysate and cell-free supernatant and the prebiotic (Fructooligosaccharides (FOS)) on the levels of P. aeruginosa QS molecules, virulence factors, biofilm density and metabolites were observed. These effects were investigated using exofactor assays, crystal violet and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach. Results showed that in comparison to untreated P. aeruginosa, the L. plantarum cell-free supernatant (5%) and FOS (2%) significantly reduced the levels of the virulence factor pyoverdine (PVD) and several metabolites in the QS pathway including Pseudomonas autoinducer-2 (PAI-2). Metabolomics study revealed that the level of different secondary metabolites involved in the biosynthesis of vitamins, amino acids and the tricarboxylic acid (TCA) cycle were also affected. L. Plantarum was found to have a higher impact on the metabolomics profile of P. aeruginosa and its QS molecules compared to FOS. Lastly, a decrease in the formation of the P. aeruginosa biofilm was observed in a time-dependent pattern upon treatment with either cell-free supernatant of L. plantarum (5%), FOS (2%) or a combination of both treatments (5% + 2%). The latter showed the highest effect with 83% reduction in biofilm density at 72 h incubation. This work highlighted the important role probiotics and prebiotics play as potential QS inhibitors for P. aeruginosa. Moreover, it demonstrated the significant role of LC-MS metabolomics for investigating the altered biochemical and QS pathways in P. aeruginosa.