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: 10704672
• 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/10704672
• 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

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.

项目概要 龋齿是一种普遍但可以预防的口腔疾病。在龋齿活跃的受试者中，有一个转变 以产酸菌和耐酸菌为主的微生物群落。变形链球菌是一种主要的 致龋病原体。共生细菌通常通过生物活性产品帮助控制变形链球菌，例如 双氧水。然而，高糖摄入，多见于龋齿高发人群 发育，可以通过碳水化合物分解代谢物抑制来抑制 H2O2 的产生，从而 破坏体内平衡​​。最近出现了几种金属钛酸盐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。它们会引发氧化应激 某些细菌并随后抑制它们。金属钛酸盐具有广泛的牙科应用潜力 由于与各种牙科材料的高相容性，包括牙科粘合剂系统、树脂复合材料、 陶瓷、金属。此外，作为光催化剂，金属钛酸盐在催化过程中不会被消耗。 反应，但可以持续发挥作用，从而提供持久的效益。我们的团队已经证明黄金 钛酸盐可以催化并产生H2O2，它可以灭活变形链球菌，但对它的影响有限 共生口腔细菌 S. gordonii 和 S. sanguinis。据推测，选择性光活化 半导体金属钛酸盐会通过 O2 还原和其他 ROS 产生外源性 H2O2 来抑制 S. 变形菌，同时为共生细菌提供优势，从而维持牙齿生物膜的稳态 从而预防龋齿。为了检验我们的假设，目标 1 将优化金属的应用条件 钛酸盐以最大限度地发挥抗菌功效的潜力。我们将测量不同种类的ROS 钛酸金与原位探针化合物的生产。然后，我们将合成半导体金属 钛酸盐增强光催化活性（即通过可见光激活，产生更多的ROS） 改善临床表现（例如美观、相容性、物理性质、稳定性和毒性）。目标2将 鉴定暴露于金属钛酸盐的变形链球菌和共生体的基因表达。转录的 变形链球菌与金属钛酸盐的谱图将通过 mRNA 测序 (RNA-seq) 和氧化 应激相关基因将受到专门监测。目标 3 将重点关注不同的多物种口腔生物膜， 尤其是在高糖条件下。首先，我们将研究金属钛酸盐对空间组织的影响 流动细胞系统中变形链球菌和共生菌双物种生物膜的结构和组成。第二， 我们将应用牙菌斑衍生的多物种微生物生物膜和变形链球菌感染的多物种口腔微生物 社区了解复杂口腔生物膜中的物种对口腔中金属钛酸盐的反应 空腔，将采用 16S rRNA 基因测序来测量成分变化。总的来说， 该研究将全面了解金属钛酸盐对形成和形成的影响。 牙科生物膜的生态学并指导有效牙科应用的开发。