Quorum sensing (QS), or bacterial cell-to-cell communication, is a key process for bacterial colonization of substrata through biofilm formation, infections, and production of virulence factors. In an ongoing investigation of bioactive secondary metabolites from Piper species, four new flavonoids (1-4), along with five known ones (5-9) were isolated from the leaves of Piper delineatum. Their stereostructures were established by spectroscopic and spectrometric methods, including 1D and 2D NMR experiments, and comparison with data reported in the literature. The compounds were screened for their ability to interfere with QS signaling in the bacterial model Vibrio harveyi. Four compounds from this series (2, 3, 6, and 7) exhibited remarkable activity in the micromolar range, being compounds 3 and 7 particularly attractive since they did not affect bacterial growth. The results suggest that these flavonoids disrupt QS-mediated bioluminescence by interaction with elements downstream LuxO in the QS circuit of V. harveyi, and also, they exhibited a strong dose-dependent inhibition of biofilm formation. The present findings shed light on the QS inhibition mechanisms of flavonoids, underlining their potential applications.
Bibliographical noteFunding Information:
We are indebted to the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2011-28883-C03-01 and CTQ2014-55888-C03-01-R; EU, FP7-REGPOT-2012-CT2012-316137-IMBRAIN; and Campus de Excelencia Internacional CEI10/00018 projects for financial support. A.J.M.-R. thanks PLOCAN for a 2+2 contract. The authors are grateful to Dr. Tom Defoirdt (University of Ghent) for his valuable advice in the experimental set-up with Vibrio harveyi.
© 2015 Elsevier Ltd. All rights reserved.
- Piper delineatum
- Quorum sensing
- Vibrio harveyi