Suppression of bacterial cell-cell signalling, biofilm formation and type III secretion system by citrus flavonoids

J Appl Microbiol. 2010 Aug;109(2):515-527. doi: 10.1111/j.1365-2672.2010.04677.x. Epub 2010 Jan 19.


Aim: This study investigated the quorum sensing, biofilm and type three secretion system (TTSS) inhibitory properties of citrus flavonoids.

Methods and results: Flavonoids were tested for their ability to inhibit quorum sensing using Vibrio harveyi reporter assay. Biofilm assays were carried out in 96-well plates. Inhibition of biofilm formation in Escherichia coli O157:H7 and V. harveyi by citrus flavonoids was measured. Furthermore, effect of naringenin on expression of V. harveyi TTSS was investigated by semi-quantitative PCR. Differential responses for different flavonoids were observed for different cell-cell signalling systems. Among the tested flavonoids, naringenin, kaempferol, quercetin and apigenin were effective antagonists of cell-cell signalling. Furthermore, these flavonoids suppressed the biofilm formation in V. harveyi and E. coli O157:H7. In addition, naringenin altered the expression of genes encoding TTSS in V. harveyi.

Conclusion: The results of the study indicate a potential modulation of bacterial cell-cell communication, E. coli O157:H7 biofilm and V. harveyi virulence, by flavonoids especially naringenin, quercetin, sinensetin and apigenin. Among the tested flavonoids, naringenin emerged as potent and possibly a nonspecific inhibitor of autoinducer-mediated cell-cell signalling. Naringenin and other flavonoids are prominent secondary metabolites present in citrus species. Therefore, citrus, being a major source of some of these flavonoids and by virtue of widely consumed fruit, may modulate the intestinal microflora.

Significance and impact of the study: Currently, a limited number of naturally occurring compounds have demonstrated their potential in inhibition of cell-cell communications; therefore, citrus flavonoids may be useful as lead compounds for the development of antipathogenic agents.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Citrus / chemistry
  • Escherichia coli O157 / drug effects
  • Escherichia coli O157 / physiology
  • Flavanones / pharmacology
  • Flavonoids / pharmacology*
  • Quorum Sensing / drug effects*
  • Signal Transduction / drug effects
  • Vibrio / drug effects
  • Vibrio / pathogenicity
  • Vibrio / physiology
  • Virulence


  • Anti-Bacterial Agents
  • Flavanones
  • Flavonoids
  • sinensetin
  • naringenin