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

Jia, Tianyuan1; Liu, Dongjing2; Bi, Xianbiao1; Li, Menglu1,2; Cai, Zhao1; Fu, Jiapeng2; Liu, Zhi2; Wu, Pengyao2; Ke, Xue2; Jia, Aiqun3; Zhang, Guoliang2; Li, Guobao2; Yang, Liang1,2,4

2022-09-14

10.3389/fmicb.2022.896687

FRONTIERS IN MICROBIOLOGY   Impact Factor & Quartile

1664-302X

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 K-1 (Phylloquinone), K-2 (Menaquinones), and K-3 (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.

aryl hydrocarbon receptor phthiocol vitamin K Pseudomonas aeruginosa Pseudomonas quinolone signal

SCI

English

First ; Corresponding

National Key R&D Program of China[2021YFA1300902] ; Guangdong Natural Science Foundation for Distinguished Young Scholar[2020B1515020003] ; Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Southern University of Science and Technology[ZDSYS20200811144002008] ; Shenzhen Science and Technology Program[KQTD20200909113758004]

Microbiology

Microbiology

WOS:000861809400001

FRONTIERS MEDIA SA

Web of Science

1.Southern Univ Sci & Technol, Sch Med, Shenzhen, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Affiliated Hosp 2, Natl Clin Res Ctr Infect Dis, Shenzhen, Peoples R China
3.Hainan Univ, Sch Pharmaceut Sci, Haikou, Peoples R China
4.Southern Univ Sci & Technol, Shenzhen Key Lab Gene Regulat & Syst Biol, Shenzhen, Peoples R China

Jia, Tianyuan,Liu, Dongjing,Bi, Xianbiao,et al. The AhR ligand phthiocol and vitamin K analogs as Pseudomonas aeruginosa quorum sensing inhibitors[J]. FRONTIERS IN MICROBIOLOGY,2022,13.

Jia, Tianyuan.,Liu, Dongjing.,Bi, Xianbiao.,Li, Menglu.,Cai, Zhao.,...&Yang, Liang.(2022).The AhR ligand phthiocol and vitamin K analogs as Pseudomonas aeruginosa quorum sensing inhibitors.FRONTIERS IN MICROBIOLOGY,13.

Jia, Tianyuan,et al."The AhR ligand phthiocol and vitamin K analogs as Pseudomonas aeruginosa quorum sensing inhibitors".FRONTIERS IN MICROBIOLOGY 13(2022).