Dominant Mutans Streptococci Genetic Strains in Caries-Active Children

龋齿活跃儿童中的显性变形链球菌遗传株

基本信息

批准号：
9136362
负责人：
CURTIS A MACHIDA
金额：
$ 10万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-15 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9136362
关键词：
Acids Affect Aftercare Age Appearance Award Caring Child Childhood Chronic Disease Complex Dental Dental Students Dental caries Dentistry Development Diagnosis Disease Effectiveness Emergency department visit Exhibits Faculty Fingerprint Fluorides Funding General Anesthesia Genetic Genetic Databases Genetic Variation Genomics Goals Growth and Development function Health Healthcare Hospitalization Individual Infusion procedures Institution Lead Learning Lesion Manuscripts Measures Mentors Oral cavity Oral health Outcome Oxygen Patients Phenotype Population Preventive Primary Dentition Principal Investigator Property Prophylactic treatment Publishing Research Research Personnel Resistance Risk Risk Factors School Dentistry Schools Site Streptococcus mutans Students Time Treatment Cost Treatment outcome United States Variant Work Xylitol abstracting antimicrobial base clinical practice cohort deciduous tooth early childhood experience genetic strain high risk innovation insight microbial microorganism outcome forecast permanent tooth point of care pre-doctoral programs restorative dentistry restorative treatment success tooth surface undergraduate student

项目摘要

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.

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，并且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）群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。在之前的工作中，我们描述了从表现出严重儿童早期龋齿 (S-ECC) 的儿童治疗前后收集的 MS 分离株 (N=828) 的遗传指纹。我们还鉴定了个体患者口腔内龋齿和非龋齿部位出现的显性 MS 遗传菌株 (N=20)，并表征了菌株的致龋特性。我们发表的研究已鉴定出 39 种 MS 遗传菌株，并发现一些患者的龋齿修复治疗导致人群转向高产酸或耐酸 MS 菌株，治疗后 1 年出现单一显性 MS 菌株。当前项目的目标是启动一个由 250 名患者组成的新队列，其中可以独立应用恢复和辅助治疗措施来确定选择性效果，确定具有不同致龋性特征的 MS 遗传株在龋损部位与非龋损部位是否会受到优先选择并开发具有明确致龋表型的 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微生物标识符。研究假设是，患有 S-ECC 的儿童可能拥有独特的 MS 遗传菌株，这些菌株在龋齿修复治疗的特定方面会经历抵抗和/或选择，这会影响治疗的有效性和长期结果。该项目的转化目标是深入了解恢复性辅助治疗实践在消除和/或减少龋齿活跃儿童中某些 MS 遗传菌株方面的功效。这项研究的意义是深远的，因为对一些 S-ECC 患者的治疗会导致显性和高致龋性 MS 遗传株的出现，可以想象，这可能会使患者面临更高的风险。这项研究具有创新性，因为它有可能根据识别的情况来预测龋齿预防治疗的结果 MS 遗传株。 OHSU 牙科学院是符合 R15 AREA 奖项资格的机构。过去 5 年里，首席研究员和合作教员团队已指导了超过 13 名牙科住院医师研究生、30 名牙科学生和 18 名本科生进行研究，我们预计 R15 奖的新学生研究人员招募将继续取得成功。