A new small molecule inhibits Streptococcus mutans biofilms in vitro and in vivo

Abstract

Aims The aim of this study is to identify new small molecules that can inhibit Streptococcus mutans biofilms by in-vitro and in-vivo model. Methods and Results We evaluated the effect of a small molecule 2-amino-imidazole/triazole conjugate (2-AI/T) on the formation of S. mutans biofilms by culturing in 96-well plates. Toxicity was assessed through cell culture and intragastrically administering to mice. The anti-biofilm and anti-caries effects were investigated in vivo. The inhibitive mechanism was detected by isobaric tag for relative and absolute quantitation (itraq) and RT-QPCR. In vitro and in vivo study revealed that 2-AI/T significantly inhibited biofilm formation of S. mutans and is more so than inhibiting planktonic cells without toxicity. The ribosome and histidine metabolism pathways of S. mutans were significantly regulated by this compound. Conclusions These results suggest that the 2-AI/T conjugate is a potent inhibitor that can be potentially developed into a new drug to treat and prevent dental caries. Significance and Impact of the Study This is the first study to use small molecule from marine natural products, to protect from dental cariesin vivo. It has potential broad range application in clinical caries prevention, or as a bioactive ingredient for food applications.

Antimicrobial effects of the ginsenoside Rh2 on monospecies and multispecies cariogenic biofilms

“…The IC50 of Rh2 against S. mutans biofilms was much lower than that of the small molecule 2‐aminoimidazole/ triazole conjugate (2‐AI/T) used in our previous study (Pan et al . ), indicating that Rh2 had stronger bactericidal activity than 2‐AI/T; therefore, we were interested in investigating Rh2 in greater detail.…”

“…Kyoto Encyclopedia of Genes and Genomes was used to identify significantly differentially expressed pathways based on the swissprot_bacteria database (Pan et al . ; Zhong et al . ).…”

“…P < 0Á05 and fold changes >1Á2 and <0Á8 were regarded as significant differences. Kyoto Encyclopedia of Genes and Genomes was used to identify significantly differentially expressed pathways based on the swissprot_bacteria database (Pan et al 2015;Zhong et al 2015).…”

“…To the best of our knowledge, to date, there have been no reports regarding the application of ginseng extracts against multispecies oral biofilms (Pan et al . ). In our previous study, we studied the effects of a series of ginsenosides on biofilms formed by major cariogenic bacteria, namely, S. mutans , Streptococcus sobrinus and Streptococcus sanguinis .…”

“…Wu et al (2011) also found that ginseng could decrease the biofilm growth of the P. aeruginosa strain PAO1, reduce the cell viability in mature biofilms and increase the susceptibility to tobramycin. To the best of our knowledge, to date, there have been no reports regarding the application of ginseng extracts against multispecies oral biofilms (Pan et al 2015). In our previous study, we studied the effects of a series of ginsenosides on biofilms formed by major cariogenic bacteria, namely, S. mutans, Streptococcus sobrinus and Streptococcus sanguinis.…”