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Curcumin and 10-undecenoic acid as natural quorum sensing inhibitors of LuxS/AI-2 of Bacillus subtilis and LasI/LasR of Pseudomonas aeruginosa

Title
Curcumin and 10-undecenoic acid as natural quorum sensing inhibitors of LuxS/AI-2 of Bacillus subtilis and LasI/LasR of Pseudomonas aeruginosa
Type
Article in International Scientific Journal
Year
2023-01-24
Authors
Inês Gomes
(Author)
FEUP
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Simões M
(Author)
FEUP
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Anabela Borges
(Author)
FEUP
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Susana Fernandes
(Author)
Other
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Journal
Vol. 165
Initial page: 112519
ISSN: 0963-9969
Publisher: Elsevier
Other information
Authenticus ID: P-00Y-0ZA
Abstract (EN): The quorum sensing (QS) system is related to cell-to-cell communication as a function of population density, which regulates several physiological functions including biofilm formation and virulence gene expression. QS inhibitors have emerged as a promising strategy to tackle virulence and biofilm development. Among a wide variety of phytochemicals, many of them have been described as QS inhibitors. Driven by their promising clues, this study aimed to identify active phytochemicals against LuxS/autoinducer-2 (AI-2) (as the universal QS system) from Bacillus subtilis and LasI/LasR (as a specific QS system) of Pseudomonas aeruginosa, through in silico analysis followed by in vitro validation. The optimized virtual screening protocols were applied to screen a phytochemical database containing 3479 drug-like compounds. The most promising phytochemicals were curcumin, pioglitazone hydrochloride, and 10-undecenoic acid. In vitro analysis corroborated the QS inhibitory activity of curcumin and 10-undecenoic acid, however, pioglitazone hydrochloride showed no relevant effect. Inhibitory effects on LuxS/AI-2 QS system triggered reduction of 33-77% by curcumin (at 1.25-5 mu g/mL) and 36-64% by 10-undecenoic acid (at 12.5-50 mu g/mL). Inhibition of LasI/LasR QS system was 21% by curcumin (at 200 mu g/mL) and 10-54% by 10-undecenoic acid (at 15.625-250 mu g/mL). In conclusion, in silico analysis allowed the identification of curcumin and, for the first time, 10-undecenoic acid (showing low cost, high availability, and low toxicity) as alternatives to counteract bacterial pathogenicity and virulence, avoiding the imposition of selective pressure usually related to classic industrial disinfection and antibiotics therapy.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 10
Documents
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Fernandes et al. 2023_FRI pdf 2455.00 KB
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