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.

项目摘要 龋齿是一种流行但可预防的口腔疾病。在龋齿活跃的受试者中， 微生物群落以产酸菌和耐酸菌为主。变形链球菌是一种主要的 致龋病原体共生细菌通常有助于控制S。通过生物活性产品（例如 过氧化氢然而，高糖消费，这是经常发现的人口与高龋齿率 发育，可以通过碳水化合物分解代谢物抑制来抑制H2 O2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， 产生活性氧物质（ROS），包括H2 O2、O2 stecOH和1 O2。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（包括牙科粘合剂系统，树脂复合材料， 陶瓷和金属。此外，作为光催化剂，金属钛酸盐在催化的光催化剂中不会被消耗。 反应，但可以持续发挥作用，从而提供持久的利益。我们的团队证明了黄金 钛酸盐能催化生成H_2O_2，H_2O_2能催化氧化硫。变异体，而对 口腔沙门氏菌gordonii和S.吸血鬼据推测，选择性光活化 半导体金属钛酸盐将从O2还原产生外源H2 O2和其它ROS以抑制S。 变形杆菌，同时给予口腔细菌优势，从而维持牙齿生物膜中的稳态 从而防止龋齿。为了验证我们的假设，目标1将优化金属的应用条件 钛酸盐以最大化抗菌功效的潜力。我们将测量不同种类的活性氧 用原位探针化合物从钛酸金制备。然后，我们将合成半导体金属 钛酸盐以增强光催化活性（即，通过可见光激活，更多的ROS生成）， 改善临床性能（例如，美学、相容性、物理性质、稳定性和毒性）。目标2将 鉴定S.变形人和变形人暴露在金属钛酸盐中。转录 S.将通过mRNA测序（RNA-seq）和氧化修饰来揭示具有金属钛酸盐的变形杆菌。 将特别监测与压力相关的基因。目标3将集中于不同的多物种口腔生物膜， 特别是在高糖条件下。首先，我们将研究金属钛酸盐对空间组织的影响 和双物种生物膜的组成。变形杆菌和大肠杆菌。第二、 我们将应用噬菌斑衍生的多物种微生物生物膜和S.变异感染的多种口腔微生物 社区了解复杂的口腔生物膜内的物种对口腔中金属钛酸盐的反应 腔，其中16 S rRNA基因测序将用于测量组成变化。总的来说， 这项研究将提供一个全面的了解金属钛酸盐的影响， 牙科生物膜的生态学和指导有效的牙科应用的发展。