Journal of King Saud University: Science (Oct 2021)
Myrtus communis and its bioactive phytoconstituent, linalool, interferes with Quorum sensing regulated virulence functions and biofilm of uropathogenic bacteria: In vitro and in silico insights
Abstract
Ever increasing spread of drug resistance among bacterial pathogens have rendered the current antibiotic therapy ineffective. Drug-resistant urinary tract infections caused by Gram negative bacterial pathogens such as Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and Serratia marcescens are considered more severe and life threatening because of strong biofilm dependent growth characteristics among majority of them. Moreover, most uropathogens coordinate their complex virulence responses via a highly structured network of cell to cell communication known as Quorum sensing (QS). Phytochemicals/bioactive extracts obtained from established ethnomedicinal plants have previously been demonstrated as effective anti-QS agent against numerous pathogenic bacteria including uropathogens. Myrtus communis (L.) (Myrtaceae) is one such plant of immense ethnomedicinal importance and has been used in traditional medicine. In the present investigation, methanolic extract of Myrtus communis (MCME) demonstrated 65% inhibition in the QS regulated violacein production in C. violaceum without affecting the growth of the bacteria. Further, the MCME interfered significantly with QS controlled virulence production in P. aeruginosa (elastase, protease, pyocyanin and chitinase) and S. marcescens (prodigiosin and protease). The leaf extract exhibited 16–74%, 31–84%, 12–66% and 19–71% inhibition of biofilm biomass of P. aeruginosa, E. coli, A. baumannii and S. marcescens respectively at the increasing concentration corresponding to MIC/16-MIC/2. GC–MS analysis revealed Linalool as one of the major bioactive compounds present in the MCME. Further, in vitro assays demonstrated QS and biofilm inhibition by sub-MICs of linalool. In silico docking and simulation studies showed that the possible mechanisms responsible for the interference of QS were AHL synthesis inhibition, antagonization of QS-regulatory proteins, and blocking of the receptor proteins. Thus, from the obtained results it is envisaged that M. communis and its bioactive compound linalool may have medicinal implications and could prove as effective therapeutic agent in combating the threat of biofilm based persistent infections caused by uropathogenic bacteria.
