A new small molecule inhibits Streptococcus mutans biofilms in vitro and in vivo.
A new small molecule inhibits Streptococcus mutans biofilms in vitro and in vivo.
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一种新的小分子可在体外和体内抑制变形链球菌生物膜。
DOI：
10.1111/jam.12940
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发表时间：
2015-11
影响因子：
4
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Pan W;Fan M;Wu H;Melander C;Liu C
本研究的目的是通过体外和体内模型来鉴定能够抑制变形链球菌生物膜的新的小分子。我们评估了小分子2-氨基咪唑/三唑缀合物（2-AI/T）对S.通过在96孔板中培养来制备变形杆菌生物膜。通过细胞培养和小鼠灌胃给药评估毒性。体内实验观察其抗生物膜和抗龋作用。采用同量异序标记相对和绝对定量法（itraq）和RT-QPCR检测其抑制机理。体内外实验结果表明，2-AI/T对S.与无毒性地抑制增殖细胞相比，核糖体代谢途径和组氨酸代谢途径。变形杆菌受该化合物的显著调节。这些结果表明，2-AI/T缀合物是一种有效的抑制剂，可以潜在地开发成治疗和预防龋齿的新药。这是第一个使用海洋天然产物中的小分子物质在体内预防龋齿的研究。它在临床防龋或作为食品应用的生物活性成分方面具有广泛的应用潜力。
The aim of this study is to identify new small molecules that can inhibit Streptococcus mutans biofilms by in-vitro and in-vivo model. 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. 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. 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.