Proof of Concept: Scardovia wiggsiae is Cariogenic in vivo

描述（由申请方提供）：虽然已证明双歧杆菌科菌种与龋齿密切相关，但有关这些菌种致龋性的信息有限。该研究项目的长期目标是减少并最终帮助预防幼儿龋齿（ECC）。该R21申请的目的是证明/反驳以下概念：被检测为与重度ECC显著相关的Scardovia wiggsiae在体内具有致龋性。中心假设是S. wiggsiae将在体内诱导牙齿脱矿质并产生龋齿，其单独起作用或与变形链球菌协同起作用。该提议的基本原理是，体内致龋潜力的证据将证明细菌与人类牙齿健康的相关性的深入研究是合理的，如果是这样，其致龋机制也是合理的。本申请的中心假设和目标的实现将通过以下两个具体目标进行测试。目的1：Scardovia wiggsiae在体内的致龋性。工作假设是Scardovia wiggsiae将在动物模型系统中定殖并诱导牙齿脱矿。将使用不同浓度的微生物对喂食致龋饲料的Sprague道利大鼠进行灌胃。将对动物进行沙门氏菌定殖和组织侵袭试验。wiggsiae，并对龋齿进行评分。目的2：斯氏菌致龋性研究。体内的变异体。两种S. wiggsiae和S.检出变异株和重度ECC。工作假设是S. wiggsiae和S.变形菌将定殖并诱导比单独的任一种更多的牙齿脱矿质。在目标2中，S. wiggsiae和S.变形杆菌诱导龋齿的能力将与组合的S. wiggsiae和S.在目标1中使用的相同动物模型中观察到变形杆菌感染。将测定试验种属定殖和组织侵入以及龋齿。目标1中的预期结果是证明一种新命名的种属的致龋性与重度ECC显著相关，目标2中的预期结果是证明S. wiggsiae与S.变种人预期的确认S。威格氏菌在体内是致龋的，这将对该领域产生重要的积极影响，因为这将表明需要进一步研究该物种与处于龋齿危险中的不同群体的关联，并确定致龋机制，基于该机制，未来改进的微生物诊断、风险评估和早期儿童龋齿的治疗。这项研究是有意义的，因为它有望使随后的确定性研究在R 01水平的基础上的假设，S。wiggsiae是人类的龋齿病原体。虽然这一提议源于与严重ECC的物种关联，但这些发现将直接应用于成人龋齿的研究，包括快速进展的冠状和根部病变。 公共卫生相关性：这项拟议的研究与公共卫生有关，因为它将证明或反驳Scardovia wiggsiae是致龋的概念。如果该物种被证明是致龋的，将其作为龋齿的风险指标进行测试将具有公共卫生相关性，这将特别有利于口腔健康差异严重/严重ECC的人群。拟议的研究是相关的NIH的使命的NIDCR（2009-2013）的战略计划的优先事项中描述的一部分，通过整合分子和临床（体内疾病模型）的方法来证明或反驳龋齿风险的诊断生物标志物（目标I-1），并检查可能导致口腔健康不平等的因素（目标IV-1）。

DESCRIPTION (provided by applicant): While it has been demonstrated that Bifidobacteriaceae species are strongly associated with dental caries, there is limited information about cariogenicity of these species. The long-term goal of this research project is to reduce and ultimately help prevent early childhood caries (ECC). The objective of this R21 application is to prove/disprove the concept that Scardovia wiggsiae, which was detected as significantly associated with severe-ECC, is cariogenic in vivo. The central hypothesis is that S. wiggsiae will induce tooth demineralization and produce caries in vivo, acting either acting alone or in synergy with Streptococcus mutans. The rationale for this proposal is that proof of cariogenic potential in vivo would justify in- depth studies of the bacterium's relevance to human dental health, and if so, its cariogenic mechanisms. The central hypothesis and accomplishment of the objective of this application will be tested with the following two specific aims. Aim 1: Cariogenicity of Scardovia wiggsiae in vivo. The working hypothesis is that Scardovia wiggsiae will colonize and induce tooth demineralization in an animal model system. Differing concentrations of the organism will be used to inoculate Sprague Dawley rats fed a cariogenic diet. Animals will be tested for colonization and tissue invasion by S. wiggsiae, and scored for caries. Aim 2: Cariogenicity of Scardovia wiggsiae with S. mutans in vivo. Significant associations between children colonized by both S. wiggsiae and S. mutans and severe-ECC were detected. The working hypothesis is that a combination of S. wiggsiae and S. mutans will colonize and induce more tooth demineralization than either species alone. In Aim 2, the ability for separate infections by S. wiggsiae and S. mutans to induce caries will be compared with a combined S. wiggsiae and S. mutans infection in the same animal model used in Aim 1. Test species colonization and tissue invasion, and dental caries will be assayed. The expected outcomes in Aim 1 will be the demonstration of cariogenicity of a newly named species significantly associated with severe-ECC, and in Aim 2 demonstration of enhanced cariogenicity by the combined infection of S. wiggsiae with S. mutans. The expected confirmation that S. wiggsiae is cario- genic in vivo would have an important positive impact on the field because it would indicate the need for further investigation into the association of the species with diverse populations at risk for caries and determining mechanism(s) of cariogenicity on which to base future improved microbial diagnosis, risk assessment and treatment for early childhood caries. The research proposed is significant because it is expected to enable subsequent definitive studies at the R01 level based on the hypothesis that S. wiggsiae is a caries pathogen in humans. While this proposal stems from species association with severe-ECC, the findings will have direct application for studies of caries in adults including rapidly progressing coronal and root lesions. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because it will prove or disprove the concept that Scardovia wiggsiae is cariogenic. If this species proves to be cariogenic, it would be of public health relevance to test it as a risk indicator for dental caries which would particularly benefit populations with oral health disparities that experience rampant/severe-ECC. The proposed research is relevant to the part of NIH's mission that is described in the priorities of the strategic plan of NIDCR (2009-2013) by integrating a molecular and clinical (in vivo disease model) approach to prove or disprove a diagnostic biomarker for caries risk (Objective I-1), and examining factors that could contribute to oral health inequality (Objective IV-1).