标题：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
摘要：AbstractEver 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 asPseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii,andSerratia marcescensare 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 ofMyrtus communis(MCME) demonstrated 65% inhibition in the QS regulated violacein production inC. violaceumwithout affecting the growth of the bacteria. Further, the MCME interfered significantly with QS controlled virulence production inP. aeruginosa(elastase, protease, pyocyanin and chitinase) andS. marcescens(prodigiosin and protease). The leaf extract exhibited 16–74%, 31–84%, 12–66% and 19–71% inhibition of biofilm biomass ofP. aeruginosa,E. coli,A. baumanniiandS. marcescensrespectively 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 vitroassays demonstrated QS and biofilm inhibition by sub-MICs of linalool.In silicodocking 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 thatM. communisand 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.
