Antonie van Leeuwenhoek

, Volume 108, Issue 2, pp 491–504 | Cite as

Isoprenyl caffeate, a major compound in manuka propolis, is a quorum-sensing inhibitor in Chromobacterium violaceum

  • Adrian Tandhyka Gemiarto
  • Nathaniel Nyakaat Ninyio
  • Siew Wei Lee
  • Joko Logis
  • Ayesha Fatima
  • Eric Wei Chiang Chan
  • Crystale Siew Ying Lim
Original Paper


The emergence of antibiotic-resistant bacterial pathogens, especially Gram-negative bacteria, has driven investigations into suppressing bacterial virulence via quorum sensing (QS) inhibition strategies instead of bactericidal and bacteriostatic approaches. Here, we investigated several bee products for potential compound(s) that exhibit significant QS inhibitory (QSI) properties at the phenotypic and molecular levels in Chromobacterium violaceum ATCC 12472 as a model organism. Manuka propolis produced the strongest violacein inhibition on C. violaceum lawn agar, while bee pollen had no detectable QSI activity and honey had bactericidal activity. Fractionated manuka propolis (pooled fraction 5 or PF5) exhibited the largest violacein inhibition zone (24.5 ± 2.5 mm) at 1 mg dry weight per disc. In C. violaceum liquid cultures, at least 450 µg/ml of manuka propolis PF5 completely inhibited violacein production. Gene expression studies of the vioABCDE operon, involved in violacein biosynthesis, showed significant (≥two-fold) down-regulation of vioA, vioD and vioE in response to manuka propolis PF5. A potential QSI compound identified in manuka propolis PF5 is a hydroxycinnamic acid-derivative, isoprenyl caffeate, with a [M−H] of 247. Complete violacein inhibition in C. violaceum liquid cultures was achieved with at least 50 µg/ml of commercial isoprenyl caffeate. In silico docking experiments suggest that isoprenyl caffeate may act as an inhibitor of the violacein biosynthetic pathway by acting as a competitor for the FAD-binding pockets of VioD and VioA. Further studies on these compounds are warranted toward the development of anti-pathogenic drugs as adjuvants to conventional antibiotic treatments, especially in antibiotic-resistant bacterial infections.


Quorum sensing inhibition Manuka propolis Isoprenyl caffeate vio operon Antibiotic resistance Chromobacterium violaceum 



This work was done with funding from UCSI University’s Faculty of Applied Sciences and the MAKNA Cancer Research Award 2012. We thank Prof. Tom Coenye for his constructive comments of the early findings of this study and helpful insights into the QSI activity of cinnamaldehyde and cinnamaldehyde derivatives. We also thank the Drug Design & Development Research Group (DDDRG) of the University of Malaya for use of the docking software.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Adrian Tandhyka Gemiarto
    • 1
    • 4
  • Nathaniel Nyakaat Ninyio
    • 1
    • 5
  • Siew Wei Lee
    • 1
  • Joko Logis
    • 1
  • Ayesha Fatima
    • 3
  • Eric Wei Chiang Chan
    • 2
  • Crystale Siew Ying Lim
    • 1
  1. 1.Department of Biotechnology, Faculty of Applied SciencesUCSI UniversityCheras, Kuala LumpurMalaysia
  2. 2.Department of Food Science and Nutrition, Faculty of Applied SciencesUCSI UniversityCheras, Kuala LumpurMalaysia
  3. 3.Faculty of Pharmaceutical SciencesUCSI UniversityKuala LumpurMalaysia
  4. 4.Comparative Genomics CentreJames Cook UniversityTownsvilleAustralia
  5. 5.Department of Microbiology, Faculty of ScienceKaduna State UniversityKadunaNigeria

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