Diaryl Urea Derivative Molecule Inhibits Cariogenic by Affecting Exopolysaccharide Synthesis, Stress Response, and Nitrogen Metabolism.

Different small molecules have been developed to target cariogenic bacteria . Based on target-based designing and screening, a novel diaryl urea derivative, 1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea (BPU), has previously been found effective in inhibiting the growth of . However, the exact mechanism remains unclear. This current study aimed to explore the antimicrobial and antibiofilm effects of BPU on and locate key enzymes and biological processes affected by the molecule molecular docking analysis and transcriptomic profile. Our results confirmed that BPU was capable of inhibiting planktonic growth as well as biofilm formation of . The virtual binding analysis predicted that the molecule had strong binding potentials with vital enzymes (3AIC and 2ZID) involved in extracellular exopolysaccharide (EPS) synthesis. The predicted inhibitive binding was further confirmed by quantification of EPS, which found a decreased amount of EPS in the biofilms. The transcriptomic profile also found differential expression of genes involved in EPS synthesis. Moreover, the transcriptomic profile implied alterations in stress response and nitrogen metabolism in treated with BPU. Examination of differentially expressed genes involved in these biological processes revealed that altered gene expression could contribute to impaired growth, biofilm formation, and competitiveness of . In conclusion, the novel diaryl urea derivative BPU can inhibit the virulence of by affecting different biological processes and serves as a potent anti-caries agent.