Anti-biofilm activities of coumarin as quorum sensing inhibitor for Porphyromonas gingivalis

Zhiyan He; Wei Jiang; Yiting Jiang; Jiachen Dong; Zhongchen Song; Jianrong Xu; Wei Zhou

doi:10.1080/20002297.2022.2055523

Anti-biofilm activities of coumarin as quorum sensing inhibitor for Porphyromonas gingivalis

J Oral Microbiol. 2022 Mar 29;14(1):2055523. doi: 10.1080/20002297.2022.2055523. eCollection 2022.

Authors

Zhiyan He¹, Wei Jiang², Yiting Jiang³, Jiachen Dong³, Zhongchen Song³, Jianrong Xu^{4

5}, Wei Zhou¹

Affiliations

¹ Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, ‎ China.
² Department of Endodontics and Operative Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China.
³ Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China.
⁴ Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine ; Shanghai, China.
⁵ Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Porphyromonas gingivalis is a keystone pathogen in periodontitis, a biofilm-mediated infection disease. This research aimed to investigate the effect of coumarin on P. gingivalis biofilm formation. We detected the antimicrobial effect on P. gingivalis planktonic growth, observed membrane structure and morphological change by TEM, and quantified membrane permeability by calcein-AM staining. The cell surface hydrophobicity, aggregation, and attachment were assessed. We also investigated different sub-MIC concentrations of coumarin on biofilm formation, and observed biofilm structureby confocal laser scanning microscopy. The biofilm-related gene expression was evaluated using real-time PCR. The results showed that coumarin inhibited P. gingivalis growth and damaged the cell morphology above 400 μM concentration. Coumarin did not affect cell surface hydrophobicity, aggregation, attachment, and the early stage of biofilm formation at sub-MIC concentrations. Still, it exhibited anti-biofilm effects for the late-stage and pre-formed biofilms dispersion. The biofilms after coumarin treatment became interspersed, and biofilm-related gene expression was downregulated. Coumarin also inhibited AI-2 activity and interacted with the HmuY protein by molecular docking analysis. Our research demonstrated that coumarin inhibited P. gingivalis biofilm formation through a quorum sensing system.

Keywords: Porphyromas gingivalis; biofilm; coumarin; periodontitis; quorum sensing inhibitor.

Grants and funding

This work was supported by a grant from the National Natural Science Foundation of China (81971299/82173798) and was partly supported by a grant from the Science and Technology Commission of Shanghai Municipality (STCSM) (no. 20ZR1431800).