Structure-activity relationship of cinnamaldehyde analogs as inhibitors of ai-2 based quorum sensing and their effect on virulence of Vibrio spp.
Open accessAbstract
BACKGROUND: Many 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 FINDINGS: By 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/SIGNIFICANCE: Several 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
3,4-dichlorocinnamaldehyde decreases the virulence of V. anguillarum, V. harveyi and V. vulnificus by affecting the DNA-binding ability of LuxR.
“Using the nematode model Caenorhabditis elegans, Brackman and colleagues [133,134] demonstrated the ability of 3,4-dichlorocinnamaldehyde to decrease the virulence of V. anguillarum, V. harveyi and V. vulnificus by affecting the DNA-binding ability of LuxR.”
From Effect of essential oils on pathogenic bacteria (2013) · cites this paper as [133]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Lead- and drug-like compounds: the rule-of-five revolution
Lipinski, C. A. (2004) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2004.11.007 · Cited by 6,339 · see citing works
Stiernagle, T. (2006) · WormBook · doi:10.1895/wormbook.1.101.1 · Cited by 2,788 · see citing works
Comparison of multiple methods for quantification of microbial biofilms grown in microtiter plates
Peeters, E., Nelis, H. J. C. F., & Coenye, T. (2007) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2007.11.010 · Cited by 1,148 · see citing works
Self-citationSurette, M. G., Miller, M. B., & Bassler, B. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.4.1639 · Cited by 980 · see citing works
Lenz, D. H., Mok, K. C., Lilley, B. N., Kulkarni, R., Wingreen, N. S., & Bassler, B. L. (2004) · Cell · doi:10.1016/j.cell.2004.06.009 · Cited by 959 · see citing works
Quorum sensing controls biofilm formation in Vibrio cholerae
Hammer, B. K., & Bassler, B. L. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03688.x · Cited by 888 · see citing works
Quorum-sensing regulators control virulence gene expression in Vibrio cholerae
Zhu, J., Miller, M. B., Vance, R. E., Dziejman, M., Bassler, B. L., & Mekalanos, J. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052694299 · Cited by 849 · see citing works
Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio harveyi
Bassler, B. L., Greenberg, E. P., & Stevens, A. M. (1997) · Journal of Bacteriology · doi:10.1128/jb.179.12.4043-4045.1997 · Cited by 757 · see citing works
Bassler, B. L., Wright, M. E., Showalter, R. E., & Silverman, M. R. (1993) · Molecular Microbiology · doi:10.1111/j.1365-2958.1993.tb01737.x · Cited by 749 · see citing works
Bassler, B. L., Wright, M. E., & Silverman, M. R. (1994) · Molecular Microbiology · doi:10.1111/j.1365-2958.1994.tb00422.x · Cited by 701 · see citing works
Utilization of operational schemes for analog synthesis in drug design
Topliss, J. G. (1972) · Journal of Medicinal Chemistry · doi:10.1021/jm00280a002 · Cited by 458 · see citing works
The major Vibrio cholerae autoinducer and its role in virulence factor production
Higgins, D. A., Pomianek, M. E., Kraml, C. M., Taylor, R. K., Semmelhack, M. F., & Bassler, B. L. (2007) · Nature · doi:10.1038/nature06284 · Cited by 456 · see citing works
Freeman, J. A., & Bassler, B. L. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01208.x · Cited by 363 · see citing works
Brackman, G., Defoirdt, T., Miyamoto, C., Bossier, P., Van Calenbergh, S., Nelis, H., & Coenye, T. (2008) · BMC Microbiology · doi:10.1186/1471-2180-8-149 · Cited by 317 · see citing works
Self-citationQuorum sensing in vibrios: Complexity for diversification
Milton, D. L. (2006) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2006.01.044 · Cited by 265 · see citing works
Freeman, J. A., & Bassler, B. L. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.3.899-906.1999 · Cited by 251 · see citing works
Subinhibitory concentrations of cinnamaldehyde interfere with quorum sensing
Niu, C., Afre, S., & Gilbert, E. S. (2006) · Letters in Applied Microbiology · doi:10.1111/j.1472-765x.2006.02001.x · Cited by 235 · see citing works
A manual method for applying the Hansch approach to drug design
Topliss, J. G. (1977) · Journal of Medicinal Chemistry · doi:10.1021/jm00214a001 · Cited by 222 · see citing works
Defoirdt, T., Crab, R., Wood, T. K., Sorgeloos, P., Verstraete, W., & Bossier, P. (2006) · Applied and Environmental Microbiology · doi:10.1128/aem.00753-06 · Cited by 188 · see citing works
Croxatto, A., Chalker, V. J., Lauritz, J., Jaß, J., Hardman, A., Williams, P. M., Cámara, M., & Milton, D. L. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.6.1617-1629.2002 · Cited by 170 · see citing works
Battistuzzi, G., Cacchi, S., & Fabrizi, G. (2003) · Organic Letters · doi:10.1021/ol034071p · Cited by 148 · see citing works
Brackman, G., Hillaert, U., Calenbergh, S. V., Nelis, H. J. C. F., & Coenye, T. (2009) · Research in Microbiology · doi:10.1016/j.resmic.2008.12.003 · Cited by 144 · see citing works
Self-citationPompeani, A. J., Irgon, J. J., Berger, M. F., et al. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06389.x · Cited by 142 · see citing works
Battistuzzi, G., Cacchi, S., & Fabrizi, G. (2003) · ChemInform · doi:10.1002/chin.200329073 · Cited by 115 · see citing works
Quorum Sensing Enhances the Stress Response in Vibrio cholerae
Joelsson, A., Kan, B., & Zhu, J. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.02804-06 · Cited by 107 · see citing works
Crystal Structure of the Vibrio cholerae Quorum-Sensing Regulatory Protein HapR
Silva, R. S. D., Kovacikova, G., Lin, W., Taylor, R. K., Skorupski, K., & Kull, F. J. (2007) · Journal of Bacteriology · doi:10.1128/jb.01807-06 · Cited by 70 · see citing works
Brackman, G., Celen, S., Baruah, K., Bossier, P., Calenbergh, S. V., Nelis, H. J. C. F., & Coenye, T. (2009) · Microbiology · doi:10.1099/mic.0.032474-0 · Cited by 68 · see citing works
Self-citationLautens, M., & Mancuso, J. (2004) · The Journal of Organic Chemistry · doi:10.1021/jo049874k · Cited by 63 · see citing works
Identification and functional analysis of vibrio vulnificus SmcR, a novel global regulator.
Lee, J. H., Rhee, J. E., Park, U., Ju, H. M., Lee, B. C., Kim, T. S., Jeong, H. S., & Choi, S. H. (2007) · PubMed · Cited by 58 · see citing works
Wu, Z., Minhas, G. S., Wen, D., et al. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm0499615 · Cited by 58 · see citing works
Kim, Y.-J., Kim, B. S., Park, Y., Choi, W., Hwang, J., Kang, B. S., Oh, T.-K., Choi, S. H., & Kim, M. H. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.100248 · Cited by 43 · see citing works
Cooper, V. S., Carlson, W. A., & LiPuma, J. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007961 · Cited by 31 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Effect of essential oils on pathogenic bacteria
Nazzaro, F., Fratianni, F., De Martino, L., Coppola, R., & De Feo, V. (2013) · Pharmaceuticals · doi:10.3390/ph6121451 · Cited by 2,186 · see citing works
“Using the nematode model Caenorhabditis elegans, Brackman and colleagues [133,134] demonstrated the ability of 3,4-dichlorocinnamaldehyde to decrease the virulence of V.”
Background
- Authors
- Brackman, G., Celen, S., Hillaert, U., Van Calenbergh, S., Cos, P., Maes, L., Nelis, H. J., & Coenye, T.
- Affiliations
- Ghent University (BE)
- University of Antwerp (BE)
- Corresponding author
- Coenye, Tom
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-01-13
- Volume
- 6
- Issue
- 1
- Pages
- e16084
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3020944
- OpenAlex
- W1987142741
- Cited by
- 136
- References
- 32
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 5 · 2023: 10 · 2022: 10 · 2021: 11 · 2020: 12 · 2019: 11 · 2018: 12 · 2017: 6 · 2016: 5 · 2015: 4 · 2014: 9 · 2013: 12 · 2012: 8
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fonds Wetenschappelijk Onderzoek
- Universiteit Gent
- Vlaamse regering
- Bijzonder Onderzoeksfonds UGent
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Vibrio bacteria research studies
- Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
- Keywords
- quorum sensing inhibition, autoinducer-2, Vibrio, LuxR, structure-activity relationship, bacterial virulence, biofilm formation, protease production, pigment production, starvation response, Vibrio anguillarum, Vibrio harveyi, Vibrio vulnificus
- MeSH terms
- Acrolein, Anti-Bacterial Agents, DNA-Binding Proteins, Homoserine, Lactones, Repressor Proteins, Structure-Activity Relationship, Vibrio, Virulence, Trans-Activators, Quorum Sensing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
