Internalization of S. mutans in vascular endothelial cells

血管内皮细胞中变形链球菌的内化

基本信息

  • 批准号:
    8703658
  • 负责人:
  • 金额:
    $ 18.75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-07-18 至 2016-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Streptococcus mutans (Sm) has long been recognized as a major pathogen of dental caries, the most common infectious disease in humans. What is much less appreciated is its role in extra-oral infections. Sm is an opportunistic pathogen frequently identified in human bacteremias and is an etiologic agent of infectious endocarditis (IE). IE, a valvular vegetation of the endothelial layer, is a serious cardiovascular disease with often fatal outcomes directly related to dental procedures. There is now strong evidence that Sm is involved in hemorrhagic stroke, which occurs when a blood vessel ruptures in the brain. Additionally, epidemiological and DNA sequencing evidence supports a contributing role of Sm to atherosclerosis. Atherosclerosis is a complex inflammatory disease afflicting medium and large sized arteries and is the leading cause of death in the USA. The commonality of these diseases is that they are diseases of the cardiovascular system. The ability of a pathogen to attach to and invade endothelial tissues has previously been shown to be required for virulence in IE and the ability to invade endothelial cells has been shown to correlate with endocardititis severity. We have previously reported that specific strains of Sm can invade human cardiovascular aortic endothelial cells (HCAEC). New data demonstrate that the HCAEC invasion phenotype correlates with the presence of a gene encoding a collagen binding protein, Cnm, and that deletion of cnm renders the strains unable to invade. Sm OMZ175, a strain that expresses Cnm, produces significant pathology compared to control mice in a mouse model of accelerated atherosclerosis. Intracellular pathogens have evolved multiple pathways and mechanisms to enter, traffic and survive within eukaryotic cells. Thus, the mode of entry plays a major role in determining bacterial fate. There are no reports about the cellular events that govern Sm entry into cells. Our overall hypothesis is that strains of Sm expressing Cnm, such as our model organism OMZ175, are able to adhere to, enter, and persist in HCAECs and that the mechanism of entry is critical to the trafficking and survival of Sm intracellularly. Our workig hypothesis to be tested in this proposed project is that invasive Sm enters endothelial cells using specific mechanisms and that Cnm plays a central role in this entry. Understanding the mechanisms that specific strains of a ubiquitous oral pathogen have acquired that expand its virulence to sites outside of the oral cavity would provide further insight into the molecular details of adhesin mediated streptococci interactions with its host. The specific aims of this application are 1) Determine the mechanism of entry of Sm into HCAEC and 2) Determine the contribution of Cnm in the entry process. Our own data and that of others indicate that invasive strains of Sm also invade oral cells and can be detected in predentate children. In addition, cnm has now been found in strains of S. sanguinis, S. suis and S. rattus. Therefore these studies will have significance beyond CVD pathology. In addition, this project would contribute information concerning the application of cnm as a biomarker for hypervirulent strains of Sm.
描述(由申请人提供):变形链球菌(Streptococcus mutans, Sm)是人类最常见的感染性疾病——龋齿的主要病原体。人们很少认识到的是它在口腔外感染中的作用。Sm是人类细菌血症中常见的机会致病菌,是感染性心内膜炎(IE)的病原。IE是一种严重的心血管疾病,通常与牙科手术直接相关。现在有强有力的证据表明,Sm与出血性中风有关,这种中风发生在大脑血管破裂时。此外,流行病学和DNA测序证据支持Sm对动脉粥样硬化的促进作用。动脉粥样硬化是一种复杂的炎症性疾病,困扰着大中型动脉,是美国主要的死亡原因。这些疾病的共同点是它们都是心血管系统的疾病。病原体附着和侵入内皮组织的能力先前已被证明是IE毒性所必需的,并且侵入内皮细胞的能力已被证明与心内膜炎的严重程度相关。我们以前报道过特定的Sm菌株可以侵入人心血管主动脉内皮细胞(HCAEC)。新的数据表明,HCAEC侵袭表型与编码胶原结合蛋白Cnm的基因存在相关,而Cnm的缺失使菌株无法入侵。Sm OMZ175是一种表达Cnm的菌株,在加速动脉粥样硬化的小鼠模型中,与对照小鼠相比,产生了显著的病理变化。细胞内病原体已经进化出多种途径和机制来进入、运输和在真核细胞内生存。因此,进入方式在决定细菌命运方面起着重要作用。没有关于控制Sm进入细胞的细胞事件的报道。我们的总体假设是,表达Cnm的Sm菌株,如我们的模式生物OMZ175,能够粘附、进入并持续存在于hcaec中,并且进入机制对Sm在细胞内的运输和存活至关重要。我们在这个项目中要验证的工作假设是,侵袭性Sm通过特定的机制进入内皮细胞,而Cnm在这一进入中起着核心作用。了解一种普遍存在的口腔病原体的特定菌株已获得将其毒力扩展到口腔外的机制,将有助于进一步了解粘附素介导的链球菌与其宿主相互作用的分子细节。本应用的具体目的是:1)确定Sm进入HCAEC的机制;2)确定Cnm在进入过程中的贡献。我们自己的数据和其他人的数据表明,Sm的侵袭性菌株也侵入口腔细胞,可以在学龄前儿童中检测到。此外,cnm现已在血链球菌、猪链球菌和鼠链球菌菌株中发现。因此,这些研究将具有超越心血管疾病病理学的意义。此外,该项目将为cnm作为Sm高毒菌株的生物标记物的应用提供信息。

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 }}

Ann Progulske-Fox其他文献

Ann Progulske-Fox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('Ann Progulske-Fox', 18)}}的其他基金

Oral Immunology/Microbiology research group annual meeting
口腔免疫学/微生物学研究组年会
  • 批准号:
    10152835
  • 财政年份:
    2021
  • 资助金额:
    $ 18.75万
  • 项目类别:
Investigating the viable but not culturable (VBNC) state in P. gingivalis
研究牙龈卟啉单胞菌的存活但不可培养 (VBNC) 状态
  • 批准号:
    10308015
  • 财政年份:
    2019
  • 资助金额:
    $ 18.75万
  • 项目类别:
Investigating the viable but not culturable (VBNC) state in P. gingivalis
研究牙龈卟啉单胞菌的存活但不可培养 (VBNC) 状态
  • 批准号:
    10531137
  • 财政年份:
    2019
  • 资助金额:
    $ 18.75万
  • 项目类别:
Investigating the viable but not culturable (VBNC) state in P. gingivalis
研究牙龈卟啉单胞菌的存活但不可培养 (VBNC) 状态
  • 批准号:
    9885383
  • 财政年份:
    2019
  • 资助金额:
    $ 18.75万
  • 项目类别:
P. gingivalis mediated disruption of autophagy in endothelial dysfunction
牙龈卟啉单胞菌介导内皮功能障碍中自噬的破坏
  • 批准号:
    8863982
  • 财政年份:
    2015
  • 资助金额:
    $ 18.75万
  • 项目类别:
P. gingivalis mediated disruption of autophagy in endothelial dysfunction
牙龈卟啉单胞菌介导内皮功能障碍中自噬的破坏
  • 批准号:
    8916212
  • 财政年份:
    2014
  • 资助金额:
    $ 18.75万
  • 项目类别:
Internalization of S. mutans in vascular endothelial cells
血管内皮细胞中变形链球菌的内化
  • 批准号:
    8583170
  • 财政年份:
    2013
  • 资助金额:
    $ 18.75万
  • 项目类别:
Interactions Between Oral Pathogens and Vascular Cells
口腔病原体与血管细胞之间的相互作用
  • 批准号:
    7932539
  • 财政年份:
    2009
  • 资助金额:
    $ 18.75万
  • 项目类别:
Invasion-Associated Bacterial Polymorphisms
入侵相关细菌多态性
  • 批准号:
    7471969
  • 财政年份:
    2008
  • 资助金额:
    $ 18.75万
  • 项目类别:
Invasion-Associated Bacterial Polymorphisms
入侵相关细菌多态性
  • 批准号:
    7616716
  • 财政年份:
    2008
  • 资助金额:
    $ 18.75万
  • 项目类别:

相似海外基金

I-Corps: Medication Adherence System
I-Corps:药物依从性系统
  • 批准号:
    2325465
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
    Standard Grant
Improving Repositioning Adherence in Home Care: Supporting Pressure Injury Care and Prevention
提高家庭护理中的重新定位依从性:支持压力损伤护理和预防
  • 批准号:
    490105
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
    Operating Grants
An innovative, AI-driven prehabilitation platform that increases adherence, enhances post-treatment outcomes by at least 50%, and provides cost savings of 95%.
%20创新、%20AI驱动%20康复%20平台%20%20增加%20依从性、%20增强%20治疗后%20结果%20by%20at%20至少%2050%、%20和%20提供%20成本%20节省%20of%2095%
  • 批准号:
    10057526
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
    Grant for R&D
CO-LEADER: Intervention to Improve Patient-Provider Communication and Medication Adherence among Patients with Systemic Lupus Erythematosus
共同领导者:改善系统性红斑狼疮患者的医患沟通和药物依从性的干预措施
  • 批准号:
    10772887
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
Nuestro Sueno: Cultural Adaptation of a Couples Intervention to Improve PAP Adherence and Sleep Health Among Latino Couples with Implications for Alzheimer’s Disease Risk
Nuestro Sueno:夫妻干预措施的文化适应,以改善拉丁裔夫妇的 PAP 依从性和睡眠健康,对阿尔茨海默病风险产生影响
  • 批准号:
    10766947
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
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:
    $ 18.75万
  • 项目类别:
Unintrusive Pediatric Logging Orthotic Adherence Device: UPLOAD
非侵入式儿科记录矫形器粘附装置:上传
  • 批准号:
    10821172
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
Antiretroviral therapy adherence and exploratory proteomics in virally suppressed people with HIV and stroke
病毒抑制的艾滋病毒和中风患者的抗逆转录病毒治疗依从性和探索性蛋白质组学
  • 批准号:
    10748465
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
Improving medication adherence and disease control for patients with multimorbidity: the role of price transparency tools
提高多病患者的药物依从性和疾病控制:价格透明度工具的作用
  • 批准号:
    10591441
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
Development and implementation of peer-facilitated decision-making and referral support to increase uptake and adherence to HIV pre-exposure prophylaxis in African Caribbean and Black communities in Ontario
制定和实施同行协助决策和转介支持,以提高非洲加勒比地区和安大略省黑人社区对艾滋病毒暴露前预防的接受和依从性
  • 批准号:
    491109
  • 财政年份:
    2023
  • 资助金额:
    $ 18.75万
  • 项目类别:
    Fellowship Programs
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了