The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Flavonoids Suppress Pseudomonas aeruginosa Virulence through Allosteric Inhibition of Quorum-sensing Receptors
Open accessAbstract
Quorum sensing is a process of cell-cell communication that bacteria use to regulate collective behaviors. Quorum sensing depends on the production, detection, and group-wide response to extracellular signal molecules called autoinducers. In many bacterial species, quorum sensing controls virulence factor production. Thus, disrupting quorum sensing is considered a promising strategy to combat bacterial pathogenicity. Several members of a family of naturally produced plant metabolites called flavonoids inhibit Pseudomonas aeruginosa biofilm formation by an unknown mechanism. Here, we explore this family of molecules further, and we demonstrate that flavonoids specifically inhibit quorum sensing via antagonism of the autoinducer-binding receptors, LasR and RhlR. Structure-activity relationship analyses demonstrate that the presence of two hydroxyl moieties in the flavone A-ring backbone are essential for potent inhibition of LasR/RhlR. Biochemical analyses reveal that the flavonoids function non-competitively to prevent LasR/RhlR DNA binding. Administration of the flavonoids to P. aeruginosa alters transcription of quorum sensing-controlled target promoters and suppresses virulence factor production, confirming their potential as anti-infectives that do not function by traditional bacteriocidal or bacteriostatic mechanisms.
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Cites
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Cited by
Fleitas Martínez, O., Cardoso, M. H., Ribeiro, S. M., & Franco, O. L. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00074 · Cited by 304
Pseudomonas aeruginosa and microbial keratitis
Hilliam, Y., Kaye, S., & Winstanley, C. (2020) · Journal of Medical Microbiology · doi:10.1099/jmm.0.001110 · Cited by 152
(2023) · doi:10.1038/s41467-023-43702-4 · Cited by 55
Metadata
- Authors
- Paczkowski, J. E., Mukherjee, S., McCready, A. R., Cong, J.-P., Aquino, C. J., Kim, H., Henke, B. R., Smith, C. D., & Bassler, B. L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 292
- Issue
- 10
- Pages
- 4064-4076
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2582365431
- Cited by
- 319
- References
- 54
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Paczkowski, J. E., Mukherjee, S., McCready, A. R., Cong, J.-P., Aquino, C. J., Kim, H., Henke, B. R., Smith, C. D., & Bassler, B. L. (2017). Flavonoids Suppress Pseudomonas aeruginosa Virulence through Allosteric Inhibition of Quorum-sensing Receptors. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m116.770552
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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