The Structural and Functional Determination of Streptococcus mutans Adherence

变形链球菌粘附的结构和功能测定

基本信息

项目摘要

Dental caries is a polymicrobial disease that affects much of the human population worldwide, where the harmony of a cooperative eco-organization shifts towards a dysbiotic framework with overrepresentation of pathogenic microorganisms, particularly by Streptococcus mutans (SM). For planktonic SM, adhesion to tooth surface and/or dental biofilms is a crucial step in the pathogenesis of dental caries, and SM has evolved (i) SM- host and (ii) SM-microbial interactions, which are mediated through its surface proteins (adhesins). SM’s adhesion mediated interactions include: (A) The recent discovery of redundant high affinity binding of SM’s adhesins to the scavenger receptor cysteine rich domains (SRCR) of the salivary glycoprotein 340 (Gp340), which promotes caries susceptibility in the SM-host interface; and (B) The revelation of SM’s adhesin required for the SM-Candida albicans (CA) biofilm formation and acid production, which enhances cariogenicity in early childhood caries in the SM-microbial interface. Together these have revealed previously unknown interactions by once thought to be well-known and well-characterized adhesins on SM. Yet the key unanswered question remains, “how does SM mediate such redundant, but specific binding to host proteins and to other microbes?” The goal of this application is to determine the specific motif(s) and/or molecular mechanism(s) that drive SM’s adherence, particularly how they enable binding to multiple ligands. Our structural and functional studies show that SM’s surface adhesins mediate these attachments primarily via two major structural domains, the V- and C-fold. We hypothesize that “the V- and C-fold present on the surface adhesins of SM mediate specific interactions through common binding motif(s) that are crucial for biofilm formation and microbial colonization”. We will address our hypothesis through three specific aims (SAs) by (a) mapping the adherence motif(s) on the V-fold (SA1) and (b) C-fold (SA2) of oral streptococcal adhesins, and (c) investigating the role of SM’s adhesins in the SM-Candida albicans (CA) interface (SA3). The results from this multi-PD/PI study will (i) Determine the binding-motif(s)/mechanisms globally adopted by the V- and C-fold among SM’s adhesins; (ii) Determine the presence of distinct and/or overlapping adherence sites for various ligands; (iii) Provide a comparative analysis of the V- and C-fold of various adhesins from mutans and viridans streptococci, revealing species-specific differences in their binding-motifs/mechanisms; (iv) Characterize the role of SM adhesins at the SM-CA interface; and (v) Elucidate alternations in the microbial ecology modulated by SM’s V- and C-folds, particularly as they relate to dental caries. Our proposed structural analyses, genetic manipulation of key adhesion motif(s) and animal model studies will determine the adherence mechanisms and address the knowledge gap on SM’s V- and C-fold, particularly their crucial role in promoting colonization and virulence. The results will enable future development of selective combinatorial therapeutics to prevent SM’s adherence to host and microbes.
龋齿是一种多微生物疾病,影响着全世界大部分人口

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ 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 }}

Champion Christdoss Selvakumar Deivanayagam其他文献

Champion Christdoss Selvakumar Deivanayagam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 }}

{{ truncateString('Champion Christdoss Selvakumar Deivanayagam', 18)}}的其他基金

The Structural and Functional Determination of Streptococcus mutans Adherence
变形链球菌粘附的结构和功能测定
  • 批准号:
    10557896
  • 财政年份:
    2020
  • 资助金额:
    $ 42.24万
  • 项目类别:
The Structural and Functional Determination of Streptococcus mutans Adherence
变形链球菌粘附的结构和功能测定
  • 批准号:
    9980560
  • 财政年份:
    2020
  • 资助金额:
    $ 42.24万
  • 项目类别:
Structural and Functional Studies on the Platelet Adherence Protein A of Streptoc
链球菌血小板粘附蛋白A的结构和功能研究
  • 批准号:
    8773556
  • 财政年份:
    2014
  • 资助金额:
    $ 42.24万
  • 项目类别:
Structural and Functional Studies on the Platelet Adherence Protein A of Streptoc
链球菌血小板粘附蛋白A的结构和功能研究
  • 批准号:
    8912358
  • 财政年份:
    2014
  • 资助金额:
    $ 42.24万
  • 项目类别:
SAG BINDING MOTIF ON ANTIGEN I/II OF STREPTOCOCCUS MUTANS
变形链球菌抗原 I/II 上的 SAG 结合基序
  • 批准号:
    8361702
  • 财政年份:
    2011
  • 资助金额:
    $ 42.24万
  • 项目类别:
Determination of the SAG Binding Motif on AgI/II of Streptococcus Mutans
变形链球菌 AgI/II 上 SAG 结合基序的测定
  • 批准号:
    7897915
  • 财政年份:
    2007
  • 资助金额:
    $ 42.24万
  • 项目类别:
Determination of the SAG Binding Motif on AgI/II of Streptococcus Mutans
变形链球菌 AgI/II 上 SAG 结合基序的测定
  • 批准号:
    7658185
  • 财政年份:
    2007
  • 资助金额:
    $ 42.24万
  • 项目类别:
Determination of the SAG Binding Motif on AgI/II of Streptococcus Mutans
变形链球菌 AgI/II 上 SAG 结合基序的测定
  • 批准号:
    8112649
  • 财政年份:
    2007
  • 资助金额:
    $ 42.24万
  • 项目类别:
Determination of the SAG Binding Motif on AgI/II of Streptococcus Mutans
变形链球菌 AgI/II 上 SAG 结合基序的测定
  • 批准号:
    7484263
  • 财政年份:
    2007
  • 资助金额:
    $ 42.24万
  • 项目类别:
Determination of the SAG Binding Motif on AgI/II of Streptococcus Mutans
变形链球菌 AgI/II 上 SAG 结合基序的测定
  • 批准号:
    7319012
  • 财政年份:
    2007
  • 资助金额:
    $ 42.24万
  • 项目类别:

相似海外基金

Pharmacy-led Transitions of Care Intervention to Address System-Level Barriers and Improve Medication Adherence in Socioeconomically Disadvantaged Populations
药房主导的护理干预转型,以解决系统层面的障碍并提高社会经济弱势群体的药物依从性
  • 批准号:
    10594350
  • 财政年份:
    2023
  • 资助金额:
    $ 42.24万
  • 项目类别:
Evaluating Centralizing Interventions to Address Low Adherence to Lung Cancer Screening Follow-up in Decentralized Settings
评估集中干预措施,以解决分散环境中肺癌筛查随访依从性低的问题
  • 批准号:
    10738120
  • 财政年份:
    2023
  • 资助金额:
    $ 42.24万
  • 项目类别:
Suubi-Mhealth: A mobile health intervention to address depression and improve ART adherence among Youth living with HIV (YLHIV) in Uganda
Suubi-Mhealth:一种移动健康干预措施,旨在解决乌干达艾滋病毒感染者 (YLHIV) 青少年的抑郁症问题并提高抗逆转录病毒疗法的依从性
  • 批准号:
    10526768
  • 财政年份:
    2022
  • 资助金额:
    $ 42.24万
  • 项目类别:
Suubi-Mhealth: A mobile health intervention to address depression and improve ART adherence among Youth living with HIV (YLHIV) in Uganda
Suubi-Mhealth:一种移动健康干预措施,旨在解决乌干达艾滋病毒感染者 (YLHIV) 青少年的抑郁症问题并提高抗逆转录病毒疗法的依从性
  • 批准号:
    10701072
  • 财政年份:
    2022
  • 资助金额:
    $ 42.24万
  • 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
  • 批准号:
    10679092
  • 财政年份:
    2021
  • 资助金额:
    $ 42.24万
  • 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
  • 批准号:
    10432133
  • 财政年份:
    2021
  • 资助金额:
    $ 42.24万
  • 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
  • 批准号:
    10327065
  • 财政年份:
    2021
  • 资助金额:
    $ 42.24万
  • 项目类别:
Leveraging Technology to Address Access and Adherence to Conventional Hospital-Based Pulmonary Rehabilitation in Veterans with COPD
利用技术解决慢性阻塞性肺病退伍军人接受和坚持传统医院肺康复的问题
  • 批准号:
    10377366
  • 财政年份:
    2019
  • 资助金额:
    $ 42.24万
  • 项目类别:
Leveraging Technology to Address Access and Adherence to Conventional Hospital-Based Pulmonary Rehabilitation in Veterans with COPD
利用技术解决慢性阻塞性肺病退伍军人接受和坚持传统医院肺康复的问题
  • 批准号:
    10574496
  • 财政年份:
    2019
  • 资助金额:
    $ 42.24万
  • 项目类别:
Targeted interventions to address the multi-level effects of gender-based violence on PrEP uptake and adherence among adolescent girls and young women in Kenya
有针对性的干预措施,以解决性别暴力对肯尼亚少女和年轻妇女接受和坚持 PrEP 的多层面影响
  • 批准号:
    9403567
  • 财政年份:
    2017
  • 资助金额:
    $ 42.24万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了