So different and still so similar: The plant compound rosmarinic acid mimics bacterial homoserine lactone quorum sensing signals

Abstract

Apart from inter-bacteria communication quorum sensing (QS) mechanisms also enable interdomain interactions. To interfere with bacterial QS, plants were found to secrete compounds; most of which of unknown identity. We have identified the plant compound rosmarinic acid (RA) to modulate Pseudomonas aeruginosa QS by binding to the RhlR QS regulator. RA was found to be a homoserine-lactone (HSL) mimic that caused agonistic effects on transcription, resulting ultimately in a stimulation of several RhlR controlled phenotypes like virulence factor synthesis or biofilm formation. Our study was initiated by in silico screening of an RhlR model with compound libraries, demonstrating that this approach is suitable to tackle a major bottleneck in signal transduction research, which is the identification of sensor protein ligands. Previous work has shown that plant compounds interfere with the function of orphan QS regulators. Our study demonstrates that this has not necessarily to be the case since RhlR forms a functional pair with the RhlI synthase. A wide range of structurally dissimilar compounds have been found to mimic HSLs suggesting that this class of QS regulators is characterized by a significant plasticity in the recognition of effector molecules. Further research will show to what extent RA impacts on QS mechanisms of other bacteria.