Effective management of biofilm-related oral infectious diseases is a global challenge. Oral biofilm presents increased resistance to antimicrobial agents and elevated virulence compared with planktonic bacteria. Antimicrobial agents, such as chlorhexidine, have proven effective in the disruption/inhibition of oral biofilm. However, the challenge of precisely and continuously eliminating the specific pathogens without disturbing the microbial ecology still exists, which is a major factor in determining the virulence of a multispecies microbial consortium and the consequent development of oral infectious diseases. Therefore, several novel approaches are being developed to inhibit biofilm virulence without necessarily inducing microbial dysbiosis of the oral cavity. Nanoparticles, such as pH-responsive enzyme-mimic nanoparticles, have been developed to specifically target the acidic niches within the oral biofilm where tooth demineralization readily occurs, in effect controlling dental caries. Quaternary ammonium salts (QAS) such as dimethylaminododecyl methacrylate (DMADDM), when incorporated into dental adhesives or resin composite, have also shown excellent and durable antimicrobial activity and thus could effectively inhibit the occurrence of secondary caries. In addition, custom-designed small molecules, natural products and their derivatives, as well as basic amino acids such as arginine, have demonstrated ecological effects by modulating the virulence of the oral biofilm without universally killing the commensal bacteria, indicating a promising approach to the management of oral infectious diseases such as dental caries and periodontal diseases. This article aims to introduce these novel approaches that have shown potential in the control of oral biofilm. These methods may be utilized in the near future to effectively promote the clinical management of oral infectious diseases and thus benefit oral health.

The ability to control the relative motions of component parts in molecules is essential for the development of molecular nanotechnology. The advent of mechanically interlocked molecules (MIMs) has enhanced significantly the opportunities for chemists to harness such motions in artificial molecular machines (AMMs). Recently, we have developed artificial molecular pumps (AMPs) capable of producing highly energetic oligo- and poly­rotaxanes with high precision. Here, we report the design, synthesis, and operation of an AMP incorporating a photo­cleavable stopper that allows for the use of orthogonal stimuli. Our approach employs a ratchet mechanism to pump a ring onto a collecting chain, forming an intermediate [2]­rotaxane. At a subsequent time, application of light triggers the release of the ring back into the bulk solution with temporal control. This process is monitored by the quenching of the fluorescence of a naphthalene-based fluorophore. This design may find application in the fabrication of molecular transporting systems with on-demand functions.

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.

Objectives. Disruption of microbial biofilms is an effective way to control dental caries. Drug resistance and side effects of the existing antimicrobials necessitate the development of novel antibacterial agents. The current study was aimed at investigating the antibacterial activities of the repurposed natural compound napabucasin against oral streptococci. Methods. The minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibition concentration, and minimum biofilm reduction concentration of Streptococcus mutans, Streptococcus gordonii, and Streptococcus sanguinis were examined by a microdilution method. Cytotoxicity of napabucasin against human oral keratinocytes, human gingival epithelia, and macrophage RAW264.7 was evaluated by CCK8 assays. The dead/live bacterium and exopolysaccharide in the napabucasin-treated multispecies biofilms were evaluated by confocal laser scanning microscopy. Microbial composition within the napabucasin-treated biofilms was further visualized by fluorescent in situ hybridization and qPCR. And the cariogenicity of napabucasin-treated biofilms was evaluated by transverse microradiography. Results. Napabucasin exhibited good antimicrobial activity against oral streptococcal planktonic cultures and biofilms but with lessened cytotoxicity as compared to chlorhexidine. Napabucasin reduced the cariogenic S. mutans and increased the proportion of the commensal S. gordonii in the multispecies biofilms. More importantly, napabucasin significantly reduced the demineralization capability of biofilms on tooth enamels. Conclusion. Napabucasin shows lessened cytotoxicity and comparable antimicrobial effects to chlorhexidine. Repurposing napabucasin may represent a promising adjuvant for the management of dental caries.

Background:The side effects of present antimicrobials like chlorhexidine (CHX) and the emergence of drug resistance necessitate the development of alternative agents to control dental caries. Aim: This study developed a novel small molecule, namely II-6s, and investigated its antimicrobial activities against common oral streptococci associated with dental caries. Methods: The susceptibility of streptococci to II-6s was evaluated by the microdilution method, time-kill assay and scanning electron microscopy. The exopolysaccharides, dead/ live bacteria and bacterial composition of the II-6s-treated Streptococcus mutans/Streptococcus gordonii/Streptococcus sanguinis 3-species biofilms were analyzed by confocal laser scanning microscopy, fluorescent in situ hybridization and quantitative PCR. The anti-demineralization effect and cytotoxicity of II-6s were evaluated by transverse microradiography and CCK-8 assay, respectively. Repeated exposure of S. mutans to II-6s was performed to assess if II-6s could induce drug resistance. Results: II-6s exhibited antimicrobial activity similar to CHX against S. mutans, S. gordonii and S. sanguinis and significantly inhibited exopolysaccharides production, live bacteria and the demineralizing capability of the 3-species streptococcal biofilms. Besides, II-6s showed reduced cytotoxicity relative to CHX and did not induce drug resistance in S. mutans after 15 passages. Conclusion: -II-6s may serve as a promising part of a successful caries management plan.