Design and assessment of novel synthetic peptides to inhibit quorum sensing-dependent biofilm formation in Pseudomonas aeruginosa

Pseudomonas aeruginosa is one of the most common biofilm-producing bacteria, often leading to long-term and chronic infections. The LasR regulator protein acts as the central regulator of the quorum sensing (QS) system and coordinates the expression of some virulence and biofilm genes. In this study, novel peptides (WSF, FASK, YDVD) were designed for binding to the domain of the transcriptional activator of the LasR protein and interfere with LasR in the QS system of P. aeruginosa. The effects of these peptides on biofilm production, expression of biofilm-related genes (AlgC, PslA, PelA), and growth of planktonic P. aeruginosa were investigated. All three peptides inhibited the growth of P. aeruginosa planktonic cells at 1600 µg ml-1 and exhibited anti-biofilm effects at sub-inhibitory concentrations (800 µg ml-1). Measurements of the mRNA levels of biofilm-related genes at sub-inhibitory concentrations of the designed peptides showed a significant decrease.