Dominant Mutans Streptococci Genetic Strains in Caries-Active Children

描述（由申请人提供）：龋齿是影响幼儿的最常见慢性疾病之一，是一种涉及危险因素复杂相互作用的多因素疾病。变形链球菌（MS）是与龋齿相关的最致龋微生物之一。我们建议确定影响儿童龋齿修复治疗后MS菌株遗传多样性和潜在选择的微生物因素。在以前的工作中，我们描述了MS分离株（N=828）治疗前和治疗后的儿童表现出严重的幼儿龋齿（S-ECC）的遗传指纹。我们还鉴定了个体患者（N=20）口腔内龋损和非龋损部位的显性MS遗传菌株，并表征了菌株的致龋性。我们发表的研究已经确定了39个MS遗传菌株，并发现在一些患者中的龋齿修复治疗导致人口转移到高度产酸或耐酸MS菌株，与单一的优势MS菌株出现在治疗后1年。本项目的目的是启动一个新的250例患者队列，其中恢复性和预防性治疗措施可以独立应用，以确定选择性效应，确定具有不同致龋性特征的MS遗传菌株是否在个体患者口腔内的龋蚀部位与非龋蚀部位进行优先选择，并开发具有明确致龋表型的MS变体的标准化遗传数据库，其可用作龋齿和治疗结果的预测性微生物标识符。研究假设S-ECC儿童可能具有不同的MS遗传菌株，在龋齿修复治疗的特定方面经历抵抗和/或选择，这影响治疗的有效性和长期结果。本项目的转化目标是提供有关恢复性和预防性治疗实践在消除和/或减少龋齿活跃儿童中某些MS遗传菌株方面的疗效的见解。这项研究的意义是深远的，因为一些S-ECC患者的治疗导致显性和高度致龋性MS遗传菌株的出现，可以想象，这可能使患者面临更高的风险。这项研究是创新的，因为它有可能预测龋齿预防治疗的结果， MS遗传菌株。OHSU牙科学院是R15区域奖的合格机构。在过去的5年里，首席研究员和协作教师小组指导了超过13名牙科研究生，30名牙科学生和18名本科生的研究，我们预计在为R15奖招募新的学生研究人员方面将继续取得成功。

DESCRIPTION (provided by applicant): Dental caries represents one of the most common chronic diseases affecting young children, and is a multi-factorial disease involving complex interactions of risk factors. The mutans streptococci (MS) group is among the most cariogenic microorganisms associated with dental caries. We propose to identify the microbial factors affecting the genetic diversity and potential selection of MS strains following caries restorative therapy in children. In prior work, we described genetic fingerprints of MS isolates (N=828) collected before and after treatment from children exhibiting severe early childhood caries (S-ECC). We have also identified the dominant MS genetic strains that occur in carious and non-carious sites within the oral cavity of individual patients (N=20), and have characterized strain cariogenicity properties. Our published studies have identified 39 MS genetic strains, and have found that caries restorative therapy in some patients results in population shifts to highly acidogenic or acid-tolerant MS strains, with single dominant MS strains appearing at 1-year post-therapy. The objectives of this current project are to initiate a new cohort of 250 patients where restorative and adjunctive therapy measures can be applied independently to ascertain selective effects, determine if MS genetic strains with distinct cariogenicity profiles undergo preferred selection in carious sites versus non-carious sites within the oral cavity of individual patients, and develop a standardized genetic database of MS variants with defined cariogenic phenotypes that may serve as predictive microbial identifiers for dental caries and treatment outcomes. The study hypothesis is that children with S-ECC may possess distinct genetic strains of MS, which undergo resistance and/or selection during specific aspects of caries restorative treatment, and this impact the effectiveness and long-term outcome of the treatment. The translational goal of this project will be to provide insight on the efficacy of restorative an adjunctive therapy practices in the elimination and/or reduction of certain MS genetic strains in caries-active children. The significance of this study is profound, as treatment in some patients with S-ECC results in the appearance of dominant and highly-cariogenic MS genetic strains, which conceivably could place the patient at even higher risk. This study is innovative because of its potential to predict the outcome of caries preventive therapy based on the identification of the MS genetic strains. The OHSU School of Dentistry is an eligible institution for an R15 AREA award. The Principal Investigator and collaborative faculty group have mentored over 13 graduate dental residents, 30 dental students and 18 undergraduate students in research over the past 5 years, and we anticipate continued success in the recruitment of new student researchers for the R15 award.