Metabolic and genetic interactions among mutans streptococci
Metabolic and genetic interactions among mutans streptococci
批准号:
9300540
负责人:
Paul Anthony Jensen
金额:
$11.03万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-03-02 至 2019-02-28
关键词:
AcidsAntibioticsAreaBacteriaBioinformaticsBiological MarkersBypassCarbonChemicalsChildClinicalCoculture TechniquesCollaborationsCommunitiesCompetenceComputational TechniqueComputer SimulationDataData SetDental ProphylaxisDental cariesDiseaseDrug TargetingEnvironmentEnzymesGene DeletionGene ExpressionGenesGeneticGenomeGenomicsGoalsGrowthImpairmentIn VitroIndividualKnowledgeLeftMapsMeasuresMetabolicMetabolismMethodsModelingMolecularMono-SOral healthOutcomeOxidasesPathway interactionsPatientsPeroxidesPhenotypePositioning AttributePreclinical Drug EvaluationProcessProductionPublicationsRattusReaderResistanceRouteSalivaSaltsSamplingShapesSourceStreptococcusStreptococcus mutansStressSystemTestingTooth DemineralizationWorkacid stressbacterial fitnessbasecomparativedesigneffective therapyenvironmental changeexperienceexperimental studyfitnessfollow-upgenetic manipulationgenetic profilinggenome analysisgenome-widein vivoinstrumentationknockout genelarge scale simulationmetabolic phenotypemetabolomicsmicrobial communitynew therapeutic targetnovelnovel therapeuticsoral bacteriaoral streptococcioverexpressionpersonalized medicinepreventprogramsquorum sensingscreeningsimulationsugartherapeutic targettherapy designtooltooth surfacetranscriptomics
中文摘要
项目概要/摘要
蛀牙(龋齿)主要是由变形链球菌产生的酸引起的,变形链球菌是一组细菌,
定居在牙齿表面。变形链球菌S.变异体,被广泛研究,
注意口腔健康。许多出版物已经描述了新陈代谢,能力,群体感应,
S.在体外和体内均存在。S.变异体很容易被操纵,
帮助我们更详细地了解细菌的遗传学。其它变形链球菌为S.索布里努斯群岛
遗传上不容易,与S相比研究不足。变种人虽然S. sobrinus殖民发生
不太常见的是,它的存在与更严重的龋齿有关,特别是在儿童中。S.远缘
临床分离物在大鼠模型中更能引起龋齿,并且S. sobrinus可以容忍
酸浓度高于S.变种人该领域的重点是S。变种人在我们的研究中留下了巨大的空白
S的知识。sobrinus,其增加致龋性的机制,以及其与S.变种人
本项目旨在通过以下方法系统地扩展我们对变异链球菌的认识:
实验和计算技术。我们将:1)进行全面的基因组学,代谢组学,
S. mutans、S. sobrinus及其相互作用; 2)发展基因组规模
细菌的代谢模型,以整合数据集和测试假设;以及3)实验映射
物种间遗传相互作用来验证和扩展我们的模型。我们的数据驱动、计算
方法将加强我们对变形链球菌之间的相似性和差异的理解。
计算机模拟基因敲除、环境变化和化学扰动的能力有助于
克服S。sobrinus对基因操作的抵抗模拟还将创建一个优先的“短-
列出了有希望的药物靶点,供后续实验使用。结合实验和计算旁路
大型、昂贵的湿实验室筛选,并为龋齿的新型治疗提供了更快的途径。
英文摘要
Project Summary/Abstract
Tooth decay (caries) is caused by acid produced primarily by the mutans streptococci, a group of bacteria that
colonize the tooth surface. The namesake of the mutans streptococci, S. mutans, is widely studied for its
detriments to oral health. Numerous publications have profiled the metabolism, competence, quorum sensing,
and acid tolerance of S. mutans, both in vitro and in vivo. The genome of S. mutans is easily manipulated,
facilitating our detailed knowledge of the bacterium's genetics. The other mutans streptococci, S. sobrinus, is
not genetically facile and is understudied compared to S. mutans. Although S. sobrinus colonization occurs
less frequently, its presence is associated with more aggressive caries, especially in children. S. sobrinus
clinical isolates are better able to cause caries in rat models, and in vitro cultures of S. sobrinus can tolerate
higher acid concentrations than S. mutans. The field's focus on S. mutans has left significant gaps in our
knowledge of S. sobrinus, its mechanism of increased cariogenicity, and its interactions with S. mutans.
This project aims to systematically expand our knowledge of the mutans streptococci through a combination of
experimental and computational techniques. We will: 1) perform a comprehensive genomic, metabolomic, and
phenotypic characterization of S. mutans, S. sobrinus, and their interactions; 2) develop genome-scale
metabolic models of the bacteria to integrate the datasets and test hypotheses; and 3) experimentally map
inter-species genetic interactions to validate and expand our models. Our data-driven, computational
approach will enhance our understanding of the similarities and differences among the mutans streptococci.
The ability to simulate gene knockouts, environmental changes, and chemical perturbations in silico helps
overcome S. sobrinus' resistance to genetic manipulation. The simulations will also create a prioritized “short-
list” of promising drug targets for follow-up experiments. Combining experiments and computation bypasses
large, expensive wet-lab screens and provides a faster path to novel treatments for dental caries.
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专著(0)
科研奖励(0)
会议论文
Microbial multi-stress responses: from intracellular networks to communities
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批准号:10204058
-
项目类别:
-
资助金额:$38.86万
-
财政年份:2020
-
负责人:Paul Anthony Jensen
-
依托单位:
Microbial multi-stress responses: from intracellular networks to communities
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批准号:10412083
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项目类别:
-
资助金额:$0.0万
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财政年份:2020
-
负责人:Paul Anthony Jensen
-
依托单位:
Microbial multi-stress responses: from intracellular networks to communities - Equipment Supplement
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批准号:10796123
-
项目类别:
-
资助金额:$24.95万
-
财政年份:2020
-
负责人:Paul Anthony Jensen
-
依托单位:
Microbial multi-stress responses: from intracellular networks to communities
-
批准号:10775337
-
项目类别:
-
资助金额:$34.17万
-
财政年份:2020
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负责人:Paul Anthony Jensen
-
依托单位:
Microbial multi-stress responses: from intracellular networks to communities
-
批准号:10029402
-
项目类别:
-
资助金额:$38.89万
-
财政年份:2020
-
负责人:Paul Anthony Jensen
-
依托单位:
Microbial multi-stress responses: from intracellular networks to communities
-
批准号:10625315
-
项目类别:
-
资助金额:$33.9万
-
财政年份:2020
-
负责人:Paul Anthony Jensen
-
依托单位:
Automated, model-guided phenotyping to identify metabolite/gene/microbe interactions
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批准号:10063870
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项目类别:
-
资助金额:$17.84万
-
财政年份:2019
-
负责人:Paul Anthony Jensen
-
依托单位:
海外基金