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A Novel Small Molecule, ZY354, Inhibits Dental Caries-Associated Oral Biofilms.

ABSTRACT: Biofilm control is a critical approach to the better management of dental caries. Antimicrobial small molecules have shown their potential in the disruption of oral biofilm and control of dental caries. The objectives of this study were to examine the antimicrobial activity and cytotoxicity of a newly designed small-molecule compound, ZY354. ZY354 was synthesized, and its cytotoxicity was evaluated in human oral keratinocytes (HOK), human gingival epithelial cells (HGE), and macrophages (RAW) by CCK-8 assays. Minimal inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), minimum biofilm inhibition concentrations (MBICs), and minimum biofilm reduction concentrations (MBRCs) of ZY354 against common oral streptococci (i.e., Streptococcus mutans, Streptococcus gordonii, and Streptococcus sanguinis) were determined by microdilution method. The exopolysaccharide (EPS)/bacterium ratio and the dead/live bacterium ratio in the ZY354-treated multispecies biofilms were determined by confocal laser scanning microscopy, and the microbial composition was visualized and quantified by fluorescent in situ hybridization and quantitative PCR (qPCR). The demineralizing activity of ZY354-treated biofilms was evaluated by transverse microradiography. The results showed that ZY354 exhibited low cytotoxicity in HOK, HGE, and RAW cells and exhibited potent antimicrobial activity against common oral streptococci. The EPS and the abundance of S. mutans were significantly reduced after ZY354 treatment, along with an increased dead/live microbial ratio in multispecies biofilms compared to the level with the nontreated control. The ZY354-treated multispecies biofilms exhibited reduced demineralizing activity at the biofilm/enamel interface. In conclusion, the small-molecule compound ZY354 exhibits low cytotoxicity and remarkable antimicrobial activity against oral streptococci, and it may have a great potential in anticaries clinical applications.

SUBMITTER: Zhang C

PROVIDER: S-EPMC6496107 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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A Novel Small Molecule, ZY354, Inhibits Dental Caries-Associated Oral Biofilms.

Zhang Chenzi C Kuang Xinyi X Zhou Yuanzheng Y Peng Xian X Guo Qiang Q Yang Tao T Zhou Xuedong X Luo Youfu Y Xu Xin X

Antimicrobial agents and chemotherapy 20190425 5

Biofilm control is a critical approach to the better management of dental caries. Antimicrobial small molecules have shown their potential in the disruption of oral biofilm and control of dental caries. The objectives of this study were to examine the antimicrobial activity and cytotoxicity of a newly designed small-molecule compound, ZY354. ZY354 was synthesized, and its cytotoxicity was evaluated in human oral keratinocytes (HOK), human gingival epithelial cells (HGE), and macrophages (RAW) by ...[more]

PMID: 30858201

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Project description:Streptococcus pneumoniae is a Gram positive bacterium that causes severe invasive infection such as pneumonia, septicemia, meningitis and otitis media especially in children, the elderly and immune-compromised patients. Pneumococcal colonization and disease is often associated with biofilm formation. Bacteria in biofilms exhibit elevated resistance both to antibiotics and to host defense systems, which often results in persistent and difficult-to-treat infections. Therefore, the ongoing treat to human health posed by pneumococcal biofilms has prompted extensive research aimed to identify alternative targets and new antimicrobial agents that are effective against bacteria biofilms. The effective anti-biofilm strategies should include inhibition of microbial adhesion to the surface and of colonization, interference with the signal molecules modulating biofilm development and the disaggregation of the biofilm matrix. In this study, we examine the effect of DAM inhibitor small molecule pyrimidine-diones on streptococcus pneumoniae D-39 strain growth (planktonic and biofilm) and evaluate the changes in global gene expression using c-DNA microarray. The microarray analysis was performed on total RNA extracted from biofilms grown in 24-well microtiter plate with 7µm/ml pyrimidine-diones small molecule and control biofilms (biofilms grown without pyrimidine-diones small molecule). To validate the results of microarray, real-time RT-PCR was performed on 12 differentially expressed genes from six different functional groups. cDNA-microarray analysis detected a total of 259 genes that were significantly differentially expressed in biofilm growth with pyrimidine-diones small molecule. 204 genes were significantly down expressed and 55 genes were significantly up expressed in biofilms grown with 7µm/ml pyrimidine-diones small molecule. Among the 204 down expressed genes, 45 were hypothetical protein encoding gene and 159 were functional protein encoding genes. Of 55 up-regulated genes 21 were hypothetical genes and 34 were functional protein encoding genes. The functional annotation showed that gene involve in fatty acid metabolism, cell division, cell cycles, DNA metabolism, cell assembly were significantly down regulated and galactose metabolism related gene were up-expressed in biofilm grown with pyrimidine-diones small molecule.

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A Novel Small Molecule, ZY354, Inhibits Dental Caries-Associated Oral Biofilms.

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A Novel Small Molecule, ZY354, Inhibits Dental Caries-Associated Oral Biofilms.

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