The potential use of glycosyl-transferase inhibitors for targeted reduction of S. mutans biofilms in dental materials.
The potential use of glycosyl-transferase inhibitors for targeted reduction of S. mutans biofilms in dental materials.
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DOI：
10.1038/s41598-023-39125-2
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发表时间：
2023-07-23
影响因子：
4.6
通讯作者：
Pfeifer, Carmem S.
中科院分区：
文献类型：
--
作者：
Scaffa, Polliana Mendes Candia;Kendall, Alexander;Icimoto, Marcelo Yudi;Fugolin, Ana Paula Piovezan;Logan, Matthew G.;DeVito-Moraes, Andre G.;Lewis, Steven H.;Zhang, Hua;Wu, Hui;Pfeifer, Carmem S.
变形链球菌是主要的口腔龋齿形成细菌，擅长通过在葡糖基转移酶（GTF）催化下合成不溶性胞外多糖（EPS）来产生“粘性”生物膜。为了避免使用广谱抗生素来对抗这些细菌，这项研究试图修改现有的EPS靶向小分子，最终目标是产生特异性靶向S的抗生物膜聚合物表面。变种人为了实现这一点，一种已知的GTF抑制剂（G43）在不同位置（9种衍生物，在50 μM下测试）用甲氧基或四甘醇取代进行修饰，以确定未来甲基丙烯酸酯官能化的潜在位点，然后针对单一物种S进行评估。变形杆菌生物膜正如预期的那样，化合物没有降低细菌活力。一般而言，具有甲氧基取代的化合物在减少EPS形成方面无效，而四乙二醇取代（G43-C3-TEG）导致不溶性EPS浓度的降低，尽管效果不如母体G43显著。这与在不同浓度的G43-C3-TEG下观察到的降低的GTF-C活性，以及随后的EPS形成减少和显著的结构变化一致。总之，该研究确定G43-C3-TEG是非杀菌的，并且可以通过减少EPS的产生来选择性地减少生物膜形成。这种分子将用于功能化材料表面，以在未来的研究中进行测试。
Streptococcus mutans is the primary oral caries-forming bacteria, adept at producing “sticky” biofilms via the synthesis of insoluble extracellular polysaccharides (EPS), catalyzed by glucosyltransferases (GTFs). To circumvent the use of broad-spectrum antibiotics to combat these bacteria, this study sought to modify existing EPS-targeting small molecules with the ultimate goal of producing anti-biofilm polymer surfaces specifically targeting S. mutans. To achieve this, a known GTF inhibitor (G43) was modified with methoxy or tetraethyleneglycol substitutions in different positions (nine derivatives, tested at 50-µM) to pinpoint potential sites for future methacrylate functionalization, and then assessed against single-species S. mutans biofilms. As expected, the compounds did not diminish the bacterial viability. In general, the compounds with methoxy substitution were not effective in reducing EPS formation, whereas the tetraethyleneglycol substitution (G43-C3-TEG) led to a decrease in the concentration of insoluble EPS, although the effect is less pronounced than for the parent G43. This aligns with the reduced GTF-C activity observed at different concentrations of G43-C3-TEG, as well as the consequent decrease in EPS formation, and notable structural changes. In summary, this study determined that G43-C3-TEG is non-bactericidal and can selectively reduce the biofilm formation, by decreasing the production of EPS. This molecule will serve to functionalize surfaces of materials to be tested in future research.
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影响因子：
3.4
作者：
Hartman AM;Jumde VR;Elgaher WAM;Te Poele EM;Dijkhuizen L;Hirsch AKH
通讯作者：
Hirsch AKH
影响因子：
9.5
作者：
Hwang, Geelsu;Koltisko, Bernard;Koo, Hyun
通讯作者：
Koo, Hyun
影响因子：
7.6
作者：
de Lucena，F. S.;Lewis，S. H.;Pfeifer，C. S.
通讯作者：
Pfeifer，C. S.
影响因子：
2.2
作者：
Gou, San-hu;Liu, Jie;Ni, Jing-man
通讯作者：
Ni, Jing-man
影响因子：
3.3
作者：
Liu，Xia;Zhang，Mengying;Yan，Meixing
通讯作者：
Yan，Meixing