State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan Universitygrid.13291.38, Chengdu, China.
Key Laboratory of Bio-Resources and Eco-Environment of the Ministry of Education, College of Life Sciences, Sichuan Universitygrid.13291.38, Chengdu, China.
Microbiol Spectr. 2022 Aug 31;10(4):e0119922. doi: 10.1128/spectrum.01199-22. Epub 2022 Jul 26.
Streptococcus mutans is known as an important oral pathogen causing dental caries, a widespread oral infectious disease. S. mutans synthesize exopolysaccharide (EPS) using glucosyltransferases (Gtfs), resulting in biofilm formation on the tooth surface. Bacterial cells in the biofilms become strongly resistant to a harsh environment, such as antibiotics and host defense mechanisms, making biofilm-based infections difficult to eliminate. Discovering novel antibiofilm agents, especially from natural products, helps to develop effective strategies against this kind of diseases. The present study investigated the inhibitory effect of shikimic acid (SA), one abundant compound derived from extract, on the biofilm formation of S. mutans. We found SA can reduce the EPS synthesized by this oral pathogen and modulate the transcription of biofilm formation related genes, leading to fewer bacterial cells in its biofilm. SA also interacted with cell membrane and membrane proteins, causing damage to bacterial cells. testing of biofilm formation on bovine teeth showed SA strongly decreased the number of S. mutans cells and the number of EPS accumulated on dental enamel surfaces. Moreover, SA exhibits almost no toxicity to human oral cells evaluated by biocompatibility assay. In conclusion, shikimic acid exhibits remarkable antibiofilm activity against S. mutans and has the potential to be further developed as a novel anticaries agent. Natural products are an important and cost-effective source for screening antimicrobial agents. Here, we identified one compound, shikimic acid, from extract, exhibiting antimicrobial activity against S. mutans proliferation. It also inhibits biofilm formation of this bacteria through decreasing Gtf expression and EPS synthesis. Furthermore, this compound exhibits no significant cytotoxicity at its MIC against S. mutans, providing evidence for its clinical application.
变形链球菌被认为是导致龋齿的重要口腔病原体,龋齿是一种广泛存在的口腔传染病。变形链球菌利用葡糖基转移酶(Gtfs)合成胞外多糖(EPS),导致在牙齿表面形成生物膜。生物膜中的细菌细胞对恶劣环境(如抗生素和宿主防御机制)具有很强的抵抗力,使基于生物膜的感染难以消除。发现新型抗生物膜剂,特别是从天然产物中发现,有助于开发针对此类疾病的有效策略。本研究调查了莽草酸(SA)对变形链球菌生物膜形成的抑制作用,SA 是一种从 提取物中衍生的丰富化合物。我们发现 SA 可以减少这种口腔病原体合成的 EPS,并调节生物膜形成相关基因的转录,从而减少生物膜中的细菌细胞数量。SA 还与细胞膜和膜蛋白相互作用,导致细菌细胞受损。在牛牙上进行的生物膜形成测试表明,SA 强烈减少了变形链球菌细胞的数量和在牙釉质表面积累的 EPS 数量。此外,通过细胞相容性测定评估,SA 对人口腔细胞几乎没有毒性。总之,莽草酸对变形链球菌表现出显著的抗生物膜活性,并有潜力进一步开发为新型抗龋剂。天然产物是筛选抗菌剂的重要且具有成本效益的来源。在这里,我们从 提取物中鉴定出一种化合物,莽草酸,具有抗变形链球菌增殖的活性。它还通过降低 Gtf 表达和 EPS 合成来抑制这种细菌的生物膜形成。此外,该化合物在其对变形链球菌的 MIC 下表现出对细胞无明显毒性,为其临床应用提供了证据。