Inhibition of Pseudomonas aeruginosa PAO1 Quorum-Sensing Network by Lawsone and Bis-lawsone Derivatives to Prevent Biofilm Formation and Virulence Factors Production

Background and purpose: Bacterial infections are treated with antibiotics, but the development of multi-drug resistant strains, which are growing at an increasing rate, is a phenomenon that threatens human societies. Therefore, alternative strategies are needed to combat infectious diseases. Today, compounds that reduce the pathogenicity of bacteria and do not interfere with their survival or growth are introduced as the next generation of antibiotics. Pseudomonas aeruginosa is one of the important and hazardous pathogens that employs its quorum-sensing network to regulate pathogenicity and virulence factors production. Here, we investigated the effect of a natural naphthoquinone compound, Lawsone (isolated from Henna), and its synthetic derivatives on the quorum-sensing system of P. aeruginosa PAO1. Materials and methods: First, the MIC of each compound was evaluated. Then, the effect of the selected compounds on biofilm formation and survival rate of biofilm sessile cells was investigated by colorimetric method. Finally, the virulence factors secretion of P. aeruginosa, including pyocyanin, pyoverdine, and protease was studied in the presence of the selected compounds. Results: The results indicated that Lawsone and NO2-481 reduced the production of P. aeruginosa biofilm by about 79% and 92%, respectively. Moreover, Lawsone and NO2-481 (at both concentrations, 250 and 125 µg/mL) decreased the viability of biofilm cells by about 70%. Furthermore, NO2-481 reduced the production of virulence factors including pyocyanin and pyoverdine by about 55% and 81%, respectively; however, it did not affect the protease production. Conclusion: NO2-481 derivative has the ability to reduce the pathogenicity of P. aeruginosa, and if it is proven to be non-cytotoxic, it can be assessed through animal and clinical studies, to be applied as an alternative compound along with antibiotics or disinfectants