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）：龋齿代表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。 Mutans链球菌（MS）组是与龋齿相关的最大的致癌微生物之一。我们建议确定影响儿童龋齿恢复治疗后MS菌株的遗传多样性和潜在选择的微生物因素。在先前的工作中，我们描述了从表现出严重的幼儿龋齿（S-ECC）的儿童治疗前后收集的MS分离株（n = 828）的遗传指纹。我们还确定了在单个患者口腔内的龋齿和非狂热部位中发生的主要MS遗传菌株（n = 20），并且具有菌株性致癌性的特征。我们已发表的研究已经确定了39毫秒的遗传菌株，并发现某些患者的龋齿恢复治疗会导致种群转移到高度酸性或耐酸的MS菌株，并在治疗后1年出现单个显性MS菌株。 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作为龋齿和治疗结果的预测微生物标识符。该研究假设是S-ECC患者可能具有MS的不同遗传菌株，在龋齿恢复治疗的特定方面会受到抵抗和/或选择，这会影响治疗的有效性和长期结果。该项目的翻译目标将是对恢复性的辅助治疗实践的有效性，以消除和/或减少龋齿活性儿童的某些MS遗传菌株。这项研究的意义是深远的，因为在某些S-ECC患者中的治疗导致出现显性且高度钙化的MS遗传菌株，这可以想象可以使患者处于更高的风险。这项研究具有创新性，因为它有潜力根据鉴定龋齿预防疗法的结果 MS遗传菌株。 OHSU牙科学校是R15地区奖的合格机构。在过去的5年中，这家首席调查员和合作教师小组在研究中指导了13多名研究生牙科居民，30名牙科学生和18名本科生研究，我们预计在招募新的学生研究人员R15奖中将继续取得成功。