Metal-titanates, novel anti-caries catalysts for modulating the virulence of cariogenic biofilms

金属钛酸盐，用于调节致龋生物膜毒力的新型抗龋催化剂

• 批准号: 10523468
• 负责人: Xuelian Huang
• 金额: $ 16.01万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-14 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10523468
• 关键词: 16S ribosomal RNA sequencing; Acids; Anti-Bacterial Agents; Award; Bacteria; Carbohydrates; Caries prevention; Cells; Ceramics; Chemistry; Clinical; Complex; Composite Resins; Consumption; Dental; Dental Materials; Dental caries; Development; Development Plans; Ecology; Esthetics; Gene Expression; Gene Expression Profile; Generations; Genes; Gold; Health; Homeostasis; Hydrogen Peroxide; In Situ; Measures; Mentorship; Metal exposure; Metals; Microbial Biofilms; Microbiology; Molecular; Monitor; Mouth Diseases; Oral cavity; Oxidative Stress; Performance; Photochemistry; Population; Positioning Attribute; Prevention strategy; Process; Production; Reaction; Reactive Oxygen Species; Repression; Research; Research Personnel; Research Project Grants; Streptococcus gordonii; Streptococcus mutans; Streptococcus sanguis; Stress; Structure; System; Testing; Therapeutic; Toxic effect; Virulence; Visible Radiation; Work; anticaries; career development; cariogenic bacteria; catalyst; commensal bacteria; dental adhesive; dental biofilm; improved; mRNA sequencing; microbial community; multidisciplinary; mutant; novel; oral biofilm; oral commensal; oral microbial community; oral microbiome; oxidation; pathogen; physical property; practical application; prevent; real time monitoring; response; sugar; transcriptome sequencing

PROJECT SUMMARY Dental caries is a prevalent but preventable oral disease. In caries-active subjects, there is a shift towards a microbial community dominated by acidogenic and acid-tolerant bacteria. Streptococcus mutans is a major cariogenic pathogen. Commensal bacteria normally help to control S. mutans via bioactive products such as H2O2. However, high-sugar consumption, which is frequently found in populations with a high rate of caries development, could inhibit the generation of H2O2 through carbohydrate catabolite repression and thereby disrupt homeostasis. Several metal titanates have recently emerged as effective green chemistry solutions to produce reactive oxygen species (ROS), including H2O2, O2˙–, ˙OH, and 1O2. They trigger oxidation stress in certain bacteria and subsequently inhibit them. Metal titanates have the potential for broad dental applications due to high compatibility with various dental materials, including dental adhesive systems, resin composites, ceramics, and metals. Furthermore, as photocatalysts, metal titanates will not be consumed in the catalyzed reaction but can act continuously, thus offering long-lasting benefits. Our group has demonstrated that gold titanate could catalyze and produce H2O2, which could inactivate S. mutans while having limited impact on commensal oral bacterial S. gordonii and S. sanguinis. It is hypothesized that selective photoactivated semiconducting metal-titanates will produce extrinsic H2O2 from O2 reduction and other ROS to inhibit S. mutans, while giving an advantage to commensal bacteria and thereby maintain homeostasis in dental biofilms and thus prevent dental caries. To test our hypothesis, Aim 1 will optimize the application conditions of metal titanates to maximize the potentials of the antibacterial efficacy. We will measure different species of ROS production from gold titanate with in situ probe compounds. Then, we will synthesize semiconducting metal titanates to enhance the photocatalytic activities (i.e., activation by visible light, more ROS generation) and improve clinical performances (e.g., esthetics, compatibility, physical property, stability, and toxicity). Aim 2 will identify the gene expressions of S. mutans and commensals exposed to metal titanates. The transcriptional profiles of S. mutans with metal titanates will be revealed by mRNA sequencing (RNA-seq) and the oxidative stress relevant genes will be specifically monitored. Aim 3 will focus on diverse multi-species oral biofilms, especially in high sugar condition. First, we will examine the effect of metal titanates on the spatial organization and composition of the dual-species biofilms of S. mutans and commensal bacteria in flow cell system. Second, we will apply plaque-derived multispecies microbial biofilms and S. mutans-infected multispecies oral microbial community to understand the response of species within complex oral biofilms to metal titanates in the oral cavity, for which 16S rRNA gene sequencing will be employed to measure the composition shift. Collectively, the study will provide a comprehensive understanding of the effects of metal titanates on the formation and ecology of dental biofilms and guide the development of an effective dental application.

项目摘要 牙科车是一种普遍但可预防的口腔疾病。在龋齿活跃的对象中，向 微生物群落以酸性和耐酸细菌为主。链球菌突变是主要的 致癌病原体。共生细菌通常有助于通过生物活性产物（例如 H2O2。但是，高糖消费量经常在汽车率高的人群中发现 开发，可以通过碳氢化分解代谢物的表达抑制H2O2的产生，从而抑制 破坏稳态。最近出现了几种金属滴虫作为有效的绿色化学解决方案 产生活性氧（ROS），包括H2O2，O2˙–，˙OH和1O2。它们触发氧化应激 某些细菌，随后抑制它们。金属滴定物具有广泛牙齿应用的潜力 由于与各种牙科材料的兼容性高，包括牙科粘合剂系统，树脂组成， 陶瓷和金属。此外，作为光催化剂，催化剂不会消耗金属滴虫 反应但可以连续起作用，从而带来持久的好处。我们的小组证明了黄金 钛酸可以催化并产生H2O2，这可能会使S. mutans失活，而对 共生口服细菌S. gordonii和S. sanguinis。假设有选择性的光活化 半导体金属 - 苯乙酸盐将从O2还原和其他ROS中产生外在的H2O2，以抑制S。 诱变，同时为共生细菌提供优势，从而维持牙齿生物膜中的体内稳态 从而防止牙科车。为了检验我们的假设，AIM 1将优化金属的应用条件 滴定剂以最大化抗菌效率的电势。我们将测量不同种类的ROS 来自原位探针化合物的黄金钛酸盐的生产。然后，我们将合成半导体金属 滴定物以增强光催化活性（即通过可见光激活，更多的ROS产生）和 改善临床表现（例如美学，兼容性，物理特性，稳定性和毒性）。 AIM 2意志 确定暴露于金属钛酸盐的巨链球菌的基因表达。转录 MRNA测序（RNA-Seq）和氧化性将揭示具有金属滴醇链球菌的曲线。 应力相关基因将被专门监测。 AIM 3将专注于潜水多物种的口服生物膜， 特别是在高糖状态下。首先，我们将研究金属滴定物对空间组织的影响 以及流动细胞系统中链球菌和共生细菌的双物种生物膜的组成。第二， 我们将应用斑块衍生的多种物种微生物生物膜和S. mutans感染的多物种口腔微生物 社区了解复杂口腔生物膜内物种对口腔中金属滴虫的反应 为此，将对16S rRNA基因测序进行腔体以测量组成移位。共同 该研究将对金属滴虫对形成的影响提供全面的理解和 牙科生物膜的生态学并指导有效牙科应用的发展。