Dominant Mutans Streptococci Genetic Strains in Caries-Active Children

描述（由申请人提供）：龋齿是影响幼儿最常见的慢性疾病之一，是一种多因素疾病，涉及危险因素的复杂相互作用。变形链球菌（MS）群是与龋齿相关的最具致龋性的微生物之一。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。在之前的工作中，我们描述了在患有严重早期儿童龋齿（S-ECC）的儿童治疗前后收集的MS分离株（N=828）的遗传指纹。我们还确定了在个体患者口腔内的龋齿和非龋齿部位（N=20）发生的显性MS遗传菌株，并表征了菌株的致龋性。我们发表的研究已经鉴定出39株MS遗传菌株，并发现一些患者的龋齿修复治疗导致人群转变为高致酸性或耐酸性MS菌株，在治疗后1年出现单一优势MS菌株。当前项目的目标是启动一个250例患者的新队列，其中恢复和辅助治疗措施可以独立应用，以确定选择性效应，确定具有不同致病性谱的MS遗传菌株是否在个体患者口腔内的龋齿部位与非龋齿部位进行优先选择。并开发具有明确的龋齿表型的MS变异的标准化遗传数据库，该数据库可作为龋齿和治疗结果的预测性微生物标识符。研究假设S-ECC患儿可能具有不同的MS遗传菌株，这些菌株在龋齿修复治疗的特定方面发生抗性和/或选择，从而影响治疗的有效性和长期结果。该项目的转化目标将是提供恢复性和辅助治疗实践在消除和/或减少某些MS遗传菌株在龋齿活跃儿童中的功效。这项研究的意义是深远的，因为在一些S-ECC患者的治疗中，出现了显性的、高致龋性的MS遗传菌株，可以想象，这可能会使患者面临更高的风险。这项研究具有创新意义，因为它有可能在识别的基础上预测龋齿预防治疗的结果

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.