Dissecting the role of sialic acid and sialidase in the pathophysiology of Porphyromonas gingivalis

剖析唾液酸和唾液酸酶在牙龈卟啉单胞菌病理生理学中的作用

基本信息

  • 批准号:
    10350709
  • 负责人:
  • 金额:
    $ 48.43万
  • 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:
    2021-02-15 至 2026-01-31
  • 项目状态:
    未结题

项目摘要

The overarching goal of this application is to investigate the role of sialidase and sialic acid in the keystone pathogen Porphyromonas gingivalis (Pg) and their contributions to the pathogenesis of periodontitis. Sialic acid (SA), a group of structurally related nine-carbon sugar acids, plays critical roles in host-pathogen interactions. On the host side, mammalian mucosal surfaces and secretions of the mouth, airway, gut, and vagina are especially sialoglycan-rich, which have a variety of biological, biophysical, antimicrobial, and immunological functions. In addition, a number of cell surface receptors (e.g., chemokine-, immunoglobulin-, and toll-like- receptors) are either sialylated or recognize sialylated ligands, which play critical roles in immune recognition and activation. On the pathogen side, many bacterial pathogens have evolved different mechanisms to target host SA for adherence, invasion, immune modulation and nutrient acquisition, thereby promoting their fitness and pathogenesis. Specifically, bacterial pathogens often use sialidases to hydrolyze host sialoglycans, compromise host immune defenses, and promote their survival in the mucosal niche. Salivary and gingival crevicular fluids contain a high concentration of SA bound to sialoglycans in various proteins such as mucins. Clinical studies indicate that sialidase activity in the oral cavity is positively associated with the severity of periodontitis; thus, it is recommended as a biomarker for periodontitis diagnosis. Accordingly, sialidases have been found in numerous oral bacteria including the keystone pathogen Porphyromonas gingivalis (Pg). Pg lacks genes to synthesize SA. Instead, it encodes a sialidase (PG0352), which is highly conserved among all genome sequenced Pg isolates. Previous studies from our group and others have shown that PG0352 plays a crucial role in Pg capsule synthesis, biofilms, stress response, innate immune responses, and virulence. However, the molecular mechanism underlying these phenotypes remains elusive. In this application, we hypothesize that Pg employs a sialidase and a SA specific transporter to scavenge host SA, which is in turn used to modify Pg cell surface molecules such as capsule and lipopolysaccharide (LPS), thereby intercepting host innate immune defenses, such as complement killing and phagocytosis of neutrophils and macrophage. To test this hypothesis, the following studies are specifically designed and will be implemented: Aim 1: To delineate the biochemical and structural features of PG0352 by using an approach of genetics, biochemistry, and crystallography; Aim 2: To investigate how Pg imports and utilizes SA by using a multidisciplinary approach of genetics, biochemistry, glycobiology, immunology, and biofilm assays; and Aim 3: To elucidate the role of PG0352 in the pathogenicity of Pg by using various in vitro and in vivo approaches. Completion of this project will not only provide mechanistic insights into understanding the role of SA and sialidase in the pathophysiology of Pg and perhaps other oral pathogens as well, but also will pave a way for future development of specific sialidase inhibitors against oral pathogens, which can provide alternatives to mitigate periodontal diseases.
这个应用的首要目标是研究唾液酸酶和唾液酸在keystone中的作用

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 }}

Chunhao Chris Li其他文献

Chunhao Chris Li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('Chunhao Chris Li', 18)}}的其他基金

Dissecting the role of sialic acid and sialidase in the pathophysiology of Porphyromonas gingivalis
剖析唾液酸和唾液酸酶在牙龈卟啉单胞菌病理生理学中的作用
  • 批准号:
    10545715
  • 财政年份:
    2021
  • 资助金额:
    $ 48.43万
  • 项目类别:
Exploring new virulence factors of the oral spirochete Treponema denticola
探索口腔螺旋体齿垢密螺旋体的新毒力因子
  • 批准号:
    10371498
  • 财政年份:
    2021
  • 资助金额:
    $ 48.43万
  • 项目类别:
Exploring New Virulence Factors of the Oral Spirochete Treponema denticola
探索口腔螺旋体齿垢密螺旋体的新毒力因子
  • 批准号:
    8703071
  • 财政年份:
    2013
  • 资助金额:
    $ 48.43万
  • 项目类别:
Exploring new virulence factors of the oral spirochete Treponema denticola
探索口腔螺旋体齿垢密螺旋体的新毒力因子
  • 批准号:
    10369723
  • 财政年份:
    2013
  • 资助金额:
    $ 48.43万
  • 项目类别:
Exploring new virulence factors of the oral spirochete Treponema denticola
探索口腔螺旋体齿垢密螺旋体的新毒力因子
  • 批准号:
    10596084
  • 财政年份:
    2013
  • 资助金额:
    $ 48.43万
  • 项目类别:
Exploring New Virulence Factors of the Oral Spirochete Treponema denticola
探索口腔螺旋体齿垢密螺旋体的新毒力因子
  • 批准号:
    8560243
  • 财政年份:
    2013
  • 资助金额:
    $ 48.43万
  • 项目类别:
Exploring new virulence factors of the oral spirochete Treponema denticola
探索口腔螺旋体齿垢密螺旋体的新毒力因子
  • 批准号:
    9762259
  • 财政年份:
    2013
  • 资助金额:
    $ 48.43万
  • 项目类别:
Exploring new virulence factors of the oral spirochete Treponema denticola
探索口腔螺旋体齿垢密螺旋体的新毒力因子
  • 批准号:
    9894788
  • 财政年份:
    2013
  • 资助金额:
    $ 48.43万
  • 项目类别:
Exploring new virulence factors of the oral spirochete Treponema denticola
探索口腔螺旋体齿垢密螺旋体的新毒力因子
  • 批准号:
    10796349
  • 财政年份:
    2013
  • 资助金额:
    $ 48.43万
  • 项目类别:
Exploring new virulence factors of the oral spirochete Treponema denticola
探索口腔螺旋体齿垢密螺旋体的新毒力因子
  • 批准号:
    10592783
  • 财政年份:
    2013
  • 资助金额:
    $ 48.43万
  • 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:
    $ 48.43万
  • 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:
    $ 48.43万
  • 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:
    $ 48.43万
  • 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:
    $ 48.43万
  • 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:
    $ 48.43万
  • 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:
    $ 48.43万
  • 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:
    $ 48.43万
  • 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:
    $ 48.43万
  • 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:
    $ 48.43万
  • 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:
    $ 48.43万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了