Research ArticleHost-Pathogen Interactions

Rosmarinic acid is a homoserine lactone mimic produced by plants that activates a bacterial quorum-sensing regulator

Sci. Signal.  05 Jan 2016:
Vol. 9, Issue 409, pp. ra1
DOI: 10.1126/scisignal.aaa8271

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Plants send out a bacterial mimic

Plants and microbes have evolved mechanisms to communicate. Corral-Lugo et al. determined that a plant compound, rosmarinic acid, bound to a protein in the bacterial quorum-sensing pathway, which bacteria use to regulate “community” interactions, such as the formation of biofilms. In vitro analysis showed that rosmarinic acid bound to RhlR, a transcriptional regulator in the quorum-sensing pathway of the plant and human pathogen Pseudomonas aeruginosa. Both reporter gene analysis and in vivo analysis of quorum-sensing responses showed that rosmarinic acid stimulated RhlR activity, thereby functioning as a mimic of the bacterial ligands. Identification of this molecular mimic has both agricultural and biomedical implications by enabling strategic disruption of bacterial communication.

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.

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