Exploring Integrative Conjugative Elements in the Biology and Ecology of Oral Streptococci
探索口腔链球菌生物学和生态学中的整合接合元件
基本信息
- 批准号:10426355
- 负责人:
- 金额:$ 13.97万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAntimicrobial ResistanceAutomobile DrivingBacteriaBacterial GenomeBiological ProcessBiological ProductsBiologyCRISPR interferenceCatalogingCellular MorphologyCenters for Disease Control and Prevention (U.S.)ChildDefectDental cariesDevelopmentDiseaseEcologyElementsEssential GenesEvolutionExcisionGene SilencingGenesGenetic MaterialsGenetic TranscriptionGenomeGenotypeGrowthHorizontal Gene TransferHumanInvestigationKnowledgeLifeMetabolicMetalloproteasesModelingNamesOperonOral healthOrganismOutcomePathogenesisPhenotypePhysiologicalPhysiologyPositioning AttributeProcessQuality of lifeRegulationStreptococcus Group BStreptococcus mutansStudy modelsTechnologyTooth LossVirulenceWorkantimicrobial drugbasefitnessfollow-upgenetic regulatory proteininsightinterestoral bacteriaoral biofilmoral microbiomeoral pathogenoral streptococcipathogenpathogenic bacteriatooltraittranscriptome
项目摘要
Project Summary
Essential genes represent the most critical components of a bacterial genome and are required for survival. In
recent years, we developed technologies that allowed us to identify and study essential genes in the dental
caries pathogen Streptococcus mutans. Through these studies we have identified several genes that have
unknown functions and yet, are clearly indispensable for the normal physiology of S. mutans. One of these
genes, that we are provisionally naming erfR (essential regulatory factor), is annotated as a transcriptional
regulator. Silencing of this gene causes severe growth and cell morphology defects, suggesting that we have
identified a new and unique regulatory component of S. mutans biology. Notably, this regulatory protein is also
present in the genome of other pathogens, including Group A and Group B streptococci. Since its discovery we
have made advances that show that ErfR regulates the expression of a putative integrative conjugative
element (ICE) known as TnSmu1. These elements participate in the horizontal transfer of genetic material, and
can carry desirable traits such as antimicrobial resistance, and virulence-associated genes. ICEs could be an
important mechanism driving genotypic and phenotypic diversity of this pathogen. However, there is little to no
in-depth characterization of these elements in Sm. To address this knowledge gap we will exploit TnSmu1 and
its regulation by ErfR as a model ICE and have developed three Specific Aims: 1) Functional analysis of
TnSmu1 essentiality and potential for horizontal transfer; 2) Identify genes and metabolic activities controlled
by TnSmu1 induction by transcriptome analysis; 3) Examine the impact of ICEs on Sm host fitness and
evolution. Combined results and conclusions from this proposal will lead to a greater understanding of the
mechanisms of erfR essentiality, TnSmu1 function and physiological effects on Sm, and the broader
distribution of these elements among Sm strains. The outcomes are expected to position erfR/TnSmu1 as an
important model for studying horizontal gene transfer by conjugation in oral bacteria. This will fill a void in our
understanding of these elements in Sm pathogenesis and their impacts on oral biofilm ecology. The proposal
will also contribute to our long-term aspirations in cataloging essential processes in Sm.
项目摘要
必需基因是细菌基因组中最关键的组成部分,是生存所必需的。在……里面
近年来,我们开发了一些技术,使我们能够识别和研究牙齿中的必要基因
龋病病原体变形链球菌。通过这些研究,我们已经确定了几个基因
然而,未知的功能显然是变形链球菌正常生理所不可缺少的。这其中的一个
基因,我们暂时命名为erfr(基本调节因子),被注释为转录
调整器。该基因的沉默会导致严重的生长和细胞形态缺陷,这表明我们有
发现了变形链球菌生物学中一种新的独特的调节成分。值得注意的是,这种调节蛋白也是
存在于其他病原体的基因组中,包括A组和B组链球菌。自从它被发现以来,我们
已经取得了一些进展,表明ErfR调节一种假定的整合结合词的表达
元素(ICE)称为TnSmu1。这些元素参与遗传物质的水平转移,并且
可以携带理想的特征,如抗菌素耐药性和毒力相关基因。冰可能是一种
该病原菌的基因多样性和表型多样性的重要机制。然而,几乎没有
这些元素在Sm中的深入表征。为了解决这一知识差距,我们将利用TnSmu1和
它被ErfR作为模型ICE进行调控,并制定了三个具体目标:1)功能分析
TnSmu1水平转移的必要性和潜力;2)识别受控制的基因和代谢活动
通过转录组分析TnSmu1的诱导;3)检测冰块对Sm宿主适合性和
进化论。综合这项提案的结果和结论,将使我们更好地理解
ErfR的重要性、TnSmu1功能和对Sm及更广泛的生理影响的机制
这些元素在Sm菌株中的分布。预计结果将把erfR/TnSmu1定位为
口腔细菌接合水平基因转移研究的重要模型。这将填补我们在
了解Sm发病机制中的这些因素及其对口腔生物膜生态的影响。这项建议
还将有助于我们在对Sm的基本流程进行编目方面的长期抱负。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Investigating CRISPR spacer targets and their impact on genomic diversification of Streptococcus mutans.
- DOI:10.3389/fgene.2022.997341
- 发表时间:2022
- 期刊:
- 影响因子:3.7
- 作者:Walker, Alejandro R. R.;Shields, Robert C. C.
- 通讯作者:Shields, Robert C. C.
Activation of TnSmu1, an integrative and conjugative element, by an ImmR-like transcriptional regulator in Streptococcus mutans.
- DOI:10.1099/mic.0.001254
- 发表时间:2022-10
- 期刊:
- 影响因子:2.8
- 作者:King, Shawn;Quick, Allison;King, Kalee;Walker, Alejandro R.;Shields, Robert C.
- 通讯作者:Shields, Robert C.
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Robert Colquhoun Shields其他文献
Robert Colquhoun Shields的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 13.97万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 13.97万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 13.97万 - 项目类别:
Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 13.97万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 13.97万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 13.97万 - 项目类别:
Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
- 批准号:
2230829 - 财政年份:2023
- 资助金额:
$ 13.97万 - 项目类别:
Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 13.97万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 13.97万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 13.97万 - 项目类别:
Grant-in-Aid for Scientific Research (C)