title: Rosmarinic acid is a homoserine lactone mimic produced by plants that activates a bacterial quorum-sensing regulator.
abstract: Quorum sensing is a bacterial communication mechanism that controls genes, enabling bacteria to live as communities, such as biofilms. Homoserine lactone (HSL) molecules function as quorum-sensing signals for Gram-negative bacteria. Plants also produce previously unidentified compounds that affect quorum sensing. We identified rosmarinic acid as a plant-derived compound that functioned as an HSL mimic. In vitro assays showed that rosmarinic acid bound to the quorum-sensing regulator RhlR of Pseudomonas aeruginosa PAO1 and competed with the bacterial ligand N-butanoyl-homoserine lactone (C4-HSL). Furthermore, rosmarinic acid stimulated a greater increase in RhlR-mediated transcription in vitro than that of C4-HSL. In P. aeruginosa, rosmarinic acid induced quorum sensing-dependent gene expression and increased biofilm formation and the production of the virulence factors pyocyanin and elastase. Because P. aeruginosa PAO1 infection induces rosmarinic acid secretion from plant roots, our results indicate that rosmarinic acid secretion is a plant defense mechanism to stimulate a premature quorum-sensing response. P. aeruginosa is a ubiquitous pathogen that infects plants and animals; therefore, identification of rosmarinic acid as an inducer of premature quorum-sensing responses may be useful in agriculture and inform human therapeutic strategies.
authors.affiliation: Department of Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas, C/ Prof. Albareda, 1, 18008 Granada, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Corral-Lugo
authors.affiliation: Department of Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas, C/ Prof. Albareda, 1, 18008 Granada, Spain.
authors.forename: Abdelali
authors.initials: A
authors.lastname: Daddaoua
authors.affiliation: Department of Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas, C/ Prof. Albareda, 1, 18008 Granada, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Department of Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas, C/ Prof. Albareda, 1, 18008 Granada, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Espinosa-Urgel
authors.affiliation: Department of Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas, C/ Prof. Albareda, 1, 18008 Granada, Spain. tino.krell@eez.csic.es.
authors.forename: Tino
authors.initials: T
authors.lastname: Krell
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002934:Cinnamates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D053630:Depsides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects / Q000235:genetics; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010944:Plants / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D053038:Quorum Sensing / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000097123:Rosmarinic Acid
chemical_list: D015107:4-Butyrolactone; D001426:Bacterial Proteins; D002934:Cinnamates; D053630:Depsides; D015534:Trans-Activators; D000097123:Rosmarinic Acid; C080365:LasR protein, Pseudomonas aeruginosa; C092312:N-butyrylhomoserine lactone; C086515:RhlR protein, Pseudomonas aeruginosa; C088386:homoserine lactone