Tracing the path of Quorum sensing molecules in cystic fibrosis mucus in a biomimetic in vitro permeability platform.

Autor: Garbero OV; Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 44bis, 10126, Turin, Italy., Sardelli L; Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 44bis, 10126, Turin, Italy., Butnarasu CS; Institute of Pharmacy Biopharmaceuticals, SupraFAB, Freie Universität Berlin, Altensteinstr 23a, 14195, Berlin, Germany., Frasca E; Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 44bis, 10126, Turin, Italy., Medana C; Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 44bis, 10126, Turin, Italy., Dal Bello F; Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 44bis, 10126, Turin, Italy., Visentin S; Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 44bis, 10126, Turin, Italy. sonja.visentin@unito.it.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Oct 29; Vol. 14 (1), pp. 25907. Date of Electronic Publication: 2024 Oct 29.
DOI: 10.1038/s41598-024-77375-w
Abstrakt: P. aeruginosa employs specific quorum sensing (QS) mechanisms to orchestrate biofilm formation, enhancing resistance to host defences. In physiological conditions, QS molecules permeate the lung environment and cellular membrane to reach the cytoplasmic Aryl Hydrocarbon Receptor (AhR) that is pivotal for activating the immune response against infection. In pathological conditions like cystic fibrosis (CF) this interkingdom communication is altered, favouring P. aeruginosa persistence and chronic infection. Here, we aim to investigate the molecular journey of QS molecules from CF-like environments to the cytoplasm by quantifying via HPLC-MS the permeability of selected QS molecules (quinolones, lactones, and phenazines) through in vitro models of the two main biological lung barriers: CF-mucus and cellular membrane. While QS molecules not activating AhR exhibit intermediate permeability through the cellular membrane model (PAMPA) (1.0-4.0 × 10 -6 cm/s), the AhR-activating molecule (pyocyanin) shows significantly higher permeability (8.6 ± 1.4 × 10 -6 cm/s). Importantly, combining the CF mucus model with PAMPA induces a 50% decrease in pyocyanin permeability, indicating a strong mucus-shielding effect with pathological implications in infection eradication. This study underscores the importance of quantitatively describing the AhR-active bacterial molecules, even in vitro, to offer new perspectives for understanding P. aeruginosa virulence mechanisms and for proposing new antibacterial therapeutic approaches.
(© 2024. The Author(s).)
Databáze: MEDLINE
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