Resolving host-guest interactions between pillararenes and homoserine lactones to restrain bacterial quorum sensing
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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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Date
2024-07-17
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Language
en
Pages
19
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Cell Reports Physical Science, Volume 5, issue 7
Abstract
Using supramolecular host molecules to hinder bacterial quorum sensing (QS) is a potential approach in circumventing antimicrobial resistance (AMR). The emergent family of pillararenes offers promising candidates for binding homoserine lactones (HSLs), signaling molecules used by gram-negative species, including WHO critical-priority antibiotic-resistant bacteria. Here, we compare seven cationic pillararenes against four HSLs, from (supra)molecular interactions to biological assays. Complexation, characterized by dye displacement assay and NMR spectroscopy, complemented by all-atom molecular dynamics (MD) simulations, was compared to effects in biological systems, studied using a bacterial HSL reporter system as well as biofilm and pyocyanin assays as models of QS-mediated virulence. HSL binding improves approximately 10-fold versus previous reports with a hydroxyl-functionalized pillararene, and a deeper-cavity host with marked preference for the longest-tailed HSL is identified. Successful HSL capture is directly reflected as impaired biofilm formation and pyocyanin production and improved healing in open wound in vivo models.Description
Publisher Copyright: © 2024 The Author(s)
Keywords
antimicrobial resistance, biofilm, displacement assay, homoserine lactones, host-guest chemistry, macrocycles, pillararenes, quorum sensing, supramolecular chemistry
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Citation
Luotonen, O I V, Osmekhina, E, Anaya-Plaza, E, Kaabel, S, Harmat, A L, Sammalkorpi, M, Jonkergouw, C, Linder, M B & Kostiainen, M A 2024, ' Resolving host-guest interactions between pillararenes and homoserine lactones to restrain bacterial quorum sensing ', Cell Reports Physical Science, vol. 5, no. 7, 102089 . https://doi.org/10.1016/j.xcrp.2024.102089
