Postbiotics of Lactobacillus casei target virulence and biofilm formation of Pseudomonas aeruginosa by modulating quorum sensing

Among various anti-virulence aspects, the efficacy of the bioactive constituents of probiotics, referred to as postbiotics, to affect quorum sensing (QS)-modulated signaling of pathogens, is considered as a safe natural approach. The present study investigated the potential QS-inhibitory activity of lyophilized postbiotics from Lactobacillus casei sub sp. casei PTCC 1608 on virulence phenotypes and biofilm of two strains and three clinical isolates of Pseudomonas aeruginosa. The effect of L. casei postbiotics (LCP) at sub-minimum inhibitory concentration on the expression of QS genes including lasR/I, rhlR/I, pqsA, pqsR and virulence genes including pelF (pellicle/biofilm glycosyltransferase PelF), lasB (elastase LasB) and toxA (exotoxin A) was evaluated. The viability of mouse fibroblastic NIH/3T3 cell line treated with sub-MICS of LCP was also investigated. Postbiotics were characterized using mass spectrometry-based analyses. The QS-attenuation effect of pure lactic acid as the major constituent of LCP was determined on P. aeruginosa strains. Neutralized postbiotics and crude bacteriocin did not exhibit any antibacterial activity. It was found that sub-MICS of LCP could more drastically attenuate the tested virulence phenotypes and biofilm formation than lactic acid. Biofilm inhibition was confirmed using scanning electron microscopy. The rhlI, rhlR, and pelF genes were down-regulated after treatment with LCP. No cytotoxicity effect was observed on NIH/3T3 cell line. The findings demonstrated that postbiotics of L. casei could reduce the virulence and biofilm development of P. aeruginosa and suggested a novel safe natural source for the expansion of anti-virulence treatments.