Novel strategy of S. mutans gcrR gene over-expression plus antibacterial dimethylaminohexadecyl methacrylate suppresses biofilm acids and reduces dental caries in rats

IF 4.6 1区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Dental Materials Pub Date : 2024-06-28 DOI:10.1016/j.dental.2024.06.018

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Abstract

Objective

Streptococcus mutans (S. mutans) is a major contributor to dental caries, with its ability to synthesize extracellular polysaccharides (EPS) and biofilms. The gcrR gene is a regulator of EPS synthesis and biofilm formation. The objectives of this study were to investigate a novel strategy of combining gcrR gene over-expression with dimethylaminohexadecyl methacrylate (DMAHDM), and to determine their in vivo efficacy in reducing caries in rats for the first time.

Methods

Two types of S. mutans were tested: Parent S. mutans; and gcrR gene over-expressed S. mutans (gcrR OE S. mutans). Bacterial minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were measured with DMAHDM and chlorhexidine (CHX). Biofilm biomass, polysaccharide, lactic acid production, live/dead staining, colony-forming units (CFUs), and metabolic activity (MTT) were evaluated. A Sprague-Dawley rat model was used with parent S. mutans and gcrR OE S. mutans colonization to determine caries-inhibition in vivo.

Results

Drug-susceptibility of gcrR OE S. mutans to DMAHDM or CHX was 2-fold higher than that of parent S. mutans. DMAHDM reduced biofilm CFU by 3–4 logs. Importantly, the combined gcrR OE S. mutans + DMAHDM dual strategy reduced biofilm CFU by 5 logs. In the rat model, the parent S. mutans group had a higher cariogenicity in dentinal (D_m) and extensive dentinal (D_x) regions. The DMAHDM + gcrR OE group reduced the D_m and D_x caries to only 20 % and 0 %, those of parent S. mutans + PBS control group (p < 0.05). The total caries severity of gcrR OE + DMAHDM group was decreased to 51 % that of parent S. mutans control (p < 0.05).

Significance

The strategy of combining S. mutans gcrR over-expression with antibacterial monomer reducing biofilm acids by 97 %, and reduced in vivo total caries in rats by 48 %. The gcrR over-expression + DMAHDM strategy is promising for a wide range of dental applications to inhibit caries and protect tooth structures.

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突变酵母菌 gcrR 基因过度表达加甲基丙烯酸二甲氨基十六烷基酯抗菌的新策略可抑制生物膜酸并减少大鼠的龋齿。

目的：变异链球菌（S. mutans）具有合成胞外多糖（EPS）和生物膜的能力，是导致龋齿的主要因素。gcrR 基因是 EPS 合成和生物膜形成的调控因子。本研究的目的是研究一种将 gcrR 基因过度表达与甲基丙烯酸二甲氨基十六烷基酯（DMAHDM）相结合的新策略，并首次确定其在减少大鼠龋齿方面的体内疗效：方法：测试了两种类型的 S. mutans：方法：测试了两种类型的变异单胞菌：原变异单胞菌和 gcrR 基因过度表达变异单胞菌（gcrR OE S. mutans）。用 DMAHDM 和洗必泰 (CHX) 测定细菌最低抑菌浓度 (MIC) 和最低杀菌浓度 (MBC)。对生物膜生物量、多糖、乳酸生成、活/死染色、菌落形成单位（CFU）和代谢活性（MTT）进行了评估。在 Sprague-Dawley 大鼠模型中使用亲本 S. mutans 和 gcrR OE S. mutans 定殖，以确定体内龋抑制作用：结果：gcrR OE S. mutans 对 DMAHDM 或 CHX 的药物敏感性是母体 S. mutans 的 2 倍。DMAHDM 可使生物膜 CFU 减少 3-4 个对数值。重要的是，结合使用 gcrR OE S. mutans+ DMAHDM 的双重策略可将生物膜 CFU 减少 5 个对数值。在大鼠模型中，母体变异杆菌组在牙本质（Dm）和广泛牙本质（Dx）区域的致龋率较高。DMAHDM + gcrR OE组将Dm龋和Dx龋的致龋率降低到仅为母体变异杆菌+PBS对照组的20%和0%（p 有学意义：变异杆菌 gcrR 过度表达与抗菌单体相结合的策略可将生物膜酸减少 97%，并将大鼠体内的总龋齿率降低 48%。gcrR 过度表达 + DMAHDM 策略有望在牙科领域广泛应用，以抑制龋齿和保护牙齿结构。

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来源期刊

Dental Materials 工程技术-材料科学：生物材料

CiteScore

9.80

自引率

10.00%

发文量

290

审稿时长

67 days

期刊介绍： Dental Materials publishes original research, review articles, and short communications. Academy of Dental Materials members click here to register for free access to Dental Materials online. The principal aim of Dental Materials is to promote rapid communication of scientific information between academia, industry, and the dental practitioner. Original Manuscripts on clinical and laboratory research of basic and applied character which focus on the properties or performance of dental materials or the reaction of host tissues to materials are given priority publication. Other acceptable topics include application technology in clinical dentistry and dental laboratory technology. Comprehensive reviews and editorial commentaries on pertinent subjects will be considered.