title: Quorum sensing inhibitory potential and molecular docking studies of sesquiterpene lactones from Vernonia blumeoides.
abstract: The increasing incidence of multidrug-resistant Gram-negative bacterial pathogens has focused research on the suppression of bacterial virulence via quorum sensing inhibition strategies, rather than the conventional antimicrobial approach. The anti-virulence potential of eudesmanolide sesquiterpene lactones previously isolated from Vernonia blumeoides was assessed by inhibition of quorum sensing and in silico molecular docking. Inhibition of quorum sensing-controlled violacein production in Chromobacterium violaceum was quantified using violacein inhibition assays. Qualitative modulation of quorum sensing activity and signal synthesis was investigated using agar diffusion double ring assays and C. violaceum and Agrobacterium tumefaciens biosensor systems. Inhibition of violacein production was concentration-dependent, with ⩾90% inhibition being obtained with ⩾2.4 mg ml(-1) of crude extracts. Violacein inhibition was significant for the ethyl acetate extract with decreasing inhibition being observed with dichloromethane, hexane and methanol extracts. Violacein inhibition ⩾80% was obtained with 0.071 mg ml(-1) of blumeoidolide B in comparison with ⩾3.6 mg ml(-1) of blumeoidolide A. Agar diffusion double ring assays indicated that only the activity of the LuxI synthase homologue, CviI, was modulated by blumeoidolides A and B, and V. blumeoides crude extracts, suggesting that quorum sensing signal synthesis was down-regulated or competitively inhibited. Finally, molecular docking was conducted to explore the binding conformations of sesquiterpene lactones into the binding sites of quorum sensing regulator proteins, CviR and CviR'. The computed binding energy data suggested that the blumeoidolides have a tendency to inhibit both CviR and CviR' with varying binding affinities. Vernonia eudesmanolide sesquiterpene lactones have the potential to be novel therapeutic agents, which might be important in reducing virulence and pathogenicity of drug-resistant bacteria in vivo.
authors.affiliation: School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
authors.forename: Abubakar Babando
authors.initials: AB
authors.lastname: Aliyu
authors.affiliation: School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
authors.forename: Neil Anthony
authors.initials: NA
authors.lastname: Koorbanally
authors.affiliation: School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
authors.forename: Brenda
authors.initials: B
authors.lastname: Moodley
authors.affiliation: School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
authors.forename: Parvesh
authors.initials: P
authors.lastname: Singh
authors.affiliation: School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Private Bag X54001, Durban 4000, South Africa. Electronic address: cheniah@ukzn.ac.za.
authors.forename: Hafizah Yousuf
authors.initials: HY
authors.lastname: Chenia
mesh_terms: D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000032:analysis / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D053038:Quorum Sensing; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D035741:Vernonia / Q000737:chemistry*
chemical_list: D007211:Indoles; D007783:Lactones; D012717:Sesquiterpenes; C000598001:blumeoidolide A; C000610801:blumeoidolide B; C476916:eudesmanolide; C063155:violacein
keywords: Asteraceae; Blumeoidolides; Molecular docking; Quorum sensing inhibition; Sesquiterpene lactones; Vernonia blumeoides