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
- 批准号:10112889
- 负责人:
- 金额:$ 42.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-03-01 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AcidsAddressAdherenceAdhesionsAdoptedAffectAffinityAnimal ModelBacterial AdhesinsBindingCandida albicansChildCollagenComplexComprehensionCoupledCrystallizationDental ModelsDental cariesDevelopmentDextransEcologyEnsureEtiologyFutureGene MutationGenesGlucansGlucosyltransferasesGoalsHumanI-antigenIndividualInvestigationKnowledgeLigandsMapsMediatingMembrane ProteinsMethodsMicrobeMicrobial BiofilmsModelingMolecularMutagenesisOralOral cavityOutcomeOutcome StudyPathogenesisPathogenicityPeptidesPlayPopulationPredispositionProductionProtein CProteinsRattusResolutionRodent ModelRoleSalivaryScavenger Receptor Cysteine-Rich DomainSiteStreptococcus Viridans GroupStreptococcus adhesinStreptococcus gordoniiStreptococcus mutansStructureStudy modelsSurfaceTherapeuticVirulencecombinatorialcomparativedental biofilmdesigndysbiosisearly childhoodgenetic manipulationglucan-binding proteinglycoprotein 340microbialmicrobial colonizationmicroorganismmicroorganism interactionmutantnanomolaroral streptococcipathogenpolymicrobial diseasepreventsortasetooth surface
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)
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Champion Christdoss Selvakumar Deivanayagam其他文献
Champion Christdoss Selvakumar Deivanayagam的其他文献
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{{ 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:
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