Pyruvate oxidase determines ecological fitness of oral streptococci

丙酮酸氧化酶决定口腔链球菌的生态适应性

• 批准号: 8631680
• 负责人: Jens Kreth
• 金额: $ 37万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-06 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8631680
• 关键词: Animals; Area; Biological; Biometry; Biophotonics; Carbohydrates; Caries prevention; Cell Aggregation; Cells; Clinical; Clinical Research; Communicable Diseases; Communities; DNA; Data; Dental; Dental caries; Development; Disease; Ecology; Engineering; Ensure; Environment; Environmental Risk Factor; Event; Exhibits; Gene Expression; Genes; Genetic Transcription; Genomics; Goals; Growth; Health; Hydrogen Peroxide; Image; Investigation; Knowledge; Learning; Link; Mediating; Microbial Biofilms; Microbiology; Modeling; Molecular Analysis; Molecular Profiling; Monitor; Mouth Diseases; Mus; National Institute of Dental and Craniofacial Research; Oral; Oral health; Play; Prevalence; Process; Production; Proteins; Pyruvate Oxidase; Regulation; Regulator Genes; Relative (related person); Research; Role; Streptococcus; Streptococcus gordonii; Streptococcus mutans; System; Testing; Time; Tooth Cell; base; disorder prevention; extracellular; fitness; improved; in vitro Model; in vivo; innovation; insight; interest; member; mutant; novel; novel strategies; oral biofilm; oral commensal; oral infection; oral streptococci; prevent; programs; public health relevance; response; tool

DESCRIPTION (provided by applicant): Streptococcus sanguinis and Streptococcus gordonii are considered health beneficial early colonizers of the oral biofilm. Their initial attachment influences subsequent biofilm development and species composition. The clinical relevant antagonism between commensals S. sanguinis and S. gordonii with cariogenic Streptococcus mutans provides the unique possibility to develop alternative strategies in oral disease prevention. Increasing S. sanguinis and S. gordonii competitiveness over cariogenic species like S. mutans could manipulate oral biofilm development towards a healthy composition. We recently identified pyruvate oxidase (SpxB) dependent hydrogen peroxide production by S. sanguinis and S. gordonii as major competitive factor in interspecies interactions with S. mutans. Furthermore, hydrogen peroxide induces the release of extracellular DNA required for biofilm formation. To better understand the role of hydrogen peroxide in these processes, we propose to: 1) elucidate the differences in the regulatory mechanisms of H2O2 production and self-compatibility by H2O2 producers, 2) elucidate the functional relationship between SpxB dependent H2O2 production, eDNA release and biofilm formation and 3) and probe ecological significance of SpxB in vivo at the host-bacterial interface in a novel murine model. This research provides an innovative approach to study the role of pyruvate oxidase dependent hydrogen peroxide production employing genomic, global transcription, protein interaction, and biostatistics data. The results of this research will provide an enhanced understanding of how environmental factors and the biofilm mode of growth in a multispecies setting influence the major competitive factor of oral commensals. Importantly, these studies directly link molecular analysis to biological significance. The goal is to use the gained information to increase oral commensal competitiveness, e.g. increasing hydrogen peroxide production under competitive conditions. This understanding should provide important new insight into the development of new strategies to prevent oral diseases.

描述（由申请人提供）：血链球菌和戈登链球菌被认为是口腔生物膜的有益健康的早期定植者。它们的初始附着影响随后的生物膜发育和物种组成。临床相关拮抗作用的研究。sanguinis和S. gordonii与致龋性变形链球菌的感染为开发口腔疾病预防的替代策略提供了独特的可能性。 增加S。sanguinis和S. gordonii的竞争力超过致龋物种如S.变形杆菌可以操纵口腔生物膜向健康组合物的发展。 我们最近确定了丙酮酸氧化酶（SpxB）依赖的过氧化氢生产的S。sanguinis和S. gordonii是种间相互作用的主要竞争因子。变异体此外，过氧化氢诱导生物膜形成所需的细胞外DNA的释放。为了更好地了解过氧化氢在这些过程中的作用，我们建议：1）阐明H2 O2生产者的H2 O2生产和自交亲和性的调节机制的差异，2）阐明SpxB依赖的H2 O2生产之间的功能关系，eDNA释放和生物膜形成和3）在新的鼠模型中在宿主-细菌界面处体内SpxB的探针生态学意义。 这项研究提供了一种创新的方法来研究丙酮酸氧化酶依赖的过氧化氢生产的作用，采用基因组，全球转录，蛋白质相互作用和生物统计学数据。这项研究的结果将提供一个更好的理解环境因素和生物膜模式的生长在多物种设置影响的主要竞争因素的口腔黏膜。 重要的是，这些研究直接将分子分析与生物学意义联系起来。目标是利用获得的信息来提高口服避孕药的竞争力，例如在竞争条件下提高过氧化氢的产量。这种理解应该为预防口腔疾病的新策略的发展提供重要的新见解。