Year-end Sale % OFF 
Abstract
BackgroundMany bacteria, including Vibrio spp., regulate virulence gene expression in a cell-density dependent way through a communication process termed quorum sensing (QS). Hence, interfering with QS could be a valuable novel antipathogenic strategy. Cinnamaldehyde has previously been shown to inhibit QS-regulated virulence by decreasing the DNA-binding ability of the QS response regulator LuxR. However, little is known about the structure-activity relationship of cinnamaldehyde analogs.Methodology/Principal FindingsBy evaluating the QS inhibitory activity of a series of cinnamaldehyde analogs, structural elements critical for autoinducer-2 QS inhibition were identified. These include an α,β unsaturated acyl group capable of reacting as Michael acceptor connected to a hydrophobic moiety and a partially negative charge. The most active cinnamaldehyde analogs were found to affect the starvation response, biofilm formation, pigment production and protease production in Vibrio spp in vitro, while exhibiting low cytotoxicity. In addition, these compounds significantly increased the survival of the nematode Caenorhabditis elegans infected with Vibrio anguillarum, Vibrio harveyi and Vibrio vulnificus.Conclusions/SignificanceSeveral new and more active cinnamaldehyde analogs were discovered and they were shown to affect Vibrio spp. virulence factor production in vitro and in vivo. Although ligands for LuxR have not been identified so far, the nature of different cinnamaldehyde analogs and their effect on the DNA binding ability of LuxR suggest that these compounds act as LuxR-ligands.
Highlights
Many bacteria, including Vibrio spp., regulate gene expression in a cell-density dependent way through a communication process termed quorum sensing (QS)
Cinnamaldehyde and cinnamaldehyde analogs do not affect bacterial growth or bioluminescence When used in concentrations up to 250 mM, cinnamaldehyde and most analogs (Fig. 1) did not affect the growth of the different Vibrio strains used in this study, the exception being 3,4-dichlorocinnamaldehyde and 4-nitro-cinnamaldehyde (MIC $100 mM and minimal inhibitory concentration (MIC) $50 mM, respectively)
None of the halogenated cinnamic acid analogs resulted in an increased QS inhibition compared to the corresponding cinnamaldehyde analog or to the unsubstituted cinnamaldehyde
Summary
Many bacteria, including Vibrio spp., regulate gene expression in a cell-density dependent way through a communication process termed quorum sensing (QS). At low population density only basal amounts of diffusible signal molecules are produced, and in this situation the receptor will act as a kinase, resulting in the phosphorylation of the downstream response regulator LuxO through a cascade involving LuxU [5]. Phosphorylation activates LuxO, resulting in the production of small regulatory RNAs [6,7]. These small RNAs, together with the chaperone protein Hfq, destabilize mRNA encoding the response regulator LuxR. Many bacteria, including Vibrio spp., regulate virulence gene expression in a cell-density dependent way through a communication process termed quorum sensing (QS). Little is known about the structure-activity relationship of cinnamaldehyde analogs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
