NDLI: The AhR ligand phthiocol and vitamin K analogs as Pseudomonas aeruginosa quorum sensing inhibitors

Content Provider	Directory of Open Access Journals (DOAJ)
Author	Tianyuan Jia Dongjing Liu Xianbiao Bi Menglu Li Zhao Cai Jiapeng Fu Zhi Liu Pengyao Wu Xue Ke Aiqun Jia Guoliang Zhang Guobao Li Liang Yang
Abstract	The aryl hydrocarbon receptor (AhR) protein senses microbial-secreted metabolites to trigger the host's innate immune system. The Pseudomonas quinolone signal (PQS) and Mycobacterium tuberculosis (MTb) metabolite phthiocol (Pht) are both ligands of AhR with similar chemical structures. As PQS is an essential quorum-sensing molecule that regulates a wide range of virulence factors in Pseudomonas aeruginosa, we hypothesized that Pht and its analogs are potential P. aeruginosa quorum-sensing inhibitors (QSIs) with immune-modulating functions. In this study, we demonstrated that Pht was able to inhibit the P. aeruginosa pqs QS system and reduce both biofilm formation and the production of pyocyanin. Molecular docking analysis suggested that Pht competes with PQS at the binding site of its receptor, PqsR. An electrophoretic mobility shift assay confirmed the Pht-PqsR interaction and showed that Pht attenuated PqsR from binding to the pqsA promoter. Proteomic analysis showed that synthesis of the key pqs QS proteins decreased upon the addition of Pht to the bacterial cultures. Furthermore, Pht analogs vitamins K1 (Phylloquinone), K2 (Menaquinones), and K3 (Menadione) were also showed to inhibit the P. aeruginosa pqs QS system while able to activate the AhR signaling pathways. Our study suggests that the AhR ligands Pht and its vitamin K analogs are promising QSIs for the alternative treatment of P. aeruginosa infections.
e-ISSN	1664302X
DOI	10.3389/fmicb.2022.896687
Journal	Frontiers in Microbiology
Volume Number	13
Language	English
Publisher	Frontiers Media S.A.
Publisher Date	2022-09-01
Publisher Place	Switzerland
Access Restriction	Open
Subject Keyword	Microbiology Aryl Hydrocarbon Receptor Phthiocol Vitamin K Pseudomonas Aeruginosa Pseudomonas Quinolone Signal
Content Type	Text
Resource Type	Article

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