Glucosylation Regulates Cyst Wall Formation, Stability, and Persistence of the AIDS Pathogen Toxoplasma gondii

糖基化调节艾滋病病原体弓形虫的囊壁形成、稳定性和持久性

基本信息

  • 批准号:
    10334999
  • 负责人:
  • 金额:
    $ 22.24万
  • 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:
    2021-09-22 至 2023-08-31
  • 项目状态:
    已结题

项目摘要

Infection by Toxoplasma gondii [Toxoplasma] is a common cause of focal central nervous system (CNS) disease in AIDS. During AIDS associated immune suppression, Toxoplasma cysts reactivate in the central nervous system (CNS) and this reactivation causes a debilitating and life-threatening Toxoplasmic encephalitis. In addition, HIV+ and AIDS patients chronically infected with Toxoplasma cysts experience accelerated deteriorating neurocognitive function. The biological basis of Toxoplasma caused disease in the CNS of HIV+ and AIDS patients is the chronic stage cyst structure that resists clearance by host immunity and maintains the viability of infectious bradyzoite stage parasites in the CNS. There currently is no therapy that can eliminate Toxoplasma cysts or prevent their reactivation and there is a significant gap in basic knowledge concerning the biology that underpins cyst persistence and cyst reactivation, particularly in HIV/AIDS and immune suppressed patients. We hypothesize that formation, stability, persistence, and reactivation of chronic stage cysts in AIDS immune suppression is dependent on an uncharacterized ~48 kDa N-acetylglucosamine modified glucosylated major cyst wall protein that binds the chitin-binding lectin succinylated wheat germ agglutinin (sWGA). The goal of this high impact exploratory R21 project is to identify the major sWGA binding glucosylated cyst wall protein(s) (Aim 1), and to conduct a series of experiments to test the hypothesis that the major glucosylated cyst wall protein is crucial for cyst wall formation, stability, persistence, and the reactivation of cysts in the CNS during AIDS defining immune suppression (Aim 2). This research is significant because O-linked sugar modification of the major cyst wall protein CST1 is known to underpin mechanisms of cyst stability, and CST1 co-localizes with the major cyst wall glucosylated protein(s). This co-localization supports the premise and hypothesis that cyst wall glucosylation supports cyst stability, and therefore cyst persistence and the ability to reactivate during AIDS. Thus, understanding how glucosylation of the cyst wall impacts cyst stability, persistence, and reactivation will further advance our basic understanding of the importance of cyst wall sugar modifications in the context of HIV/AIDS immune deficiency.
弓形虫感染是局灶性中枢神经系统(CNS)疾病的常见原因

项目成果

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DAVID J BZIK其他文献

DAVID J BZIK的其他文献

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{{ truncateString('DAVID J BZIK', 18)}}的其他基金

Metabolic basis for the persistence of dormant Toxoplasma gondii infection
休眠弓形虫感染持续存在的代谢基础
  • 批准号:
    10562309
  • 财政年份:
    2022
  • 资助金额:
    $ 22.24万
  • 项目类别:
Glucosylation Regulates Cyst Wall Formation, Stability, and Persistence of the AIDS Pathogen Toxoplasma gondii
糖基化调节艾滋病病原体弓形虫的囊壁形成、稳定性和持久性
  • 批准号:
    10493386
  • 财政年份:
    2021
  • 资助金额:
    $ 22.24万
  • 项目类别:
Iron regulation of chronic Toxoplasma gondii infection and immunity
铁对慢性弓形虫感染和免疫的调节
  • 批准号:
    10362711
  • 财政年份:
    2021
  • 资助金额:
    $ 22.24万
  • 项目类别:
Intravacuolar network dense granule protein biology in chronic Toxoplasma infection
慢性弓形虫感染中的液泡内网络致密颗粒蛋白生物学
  • 批准号:
    10084815
  • 财政年份:
    2020
  • 资助金额:
    $ 22.24万
  • 项目类别:
Novel vacuole biology in chronic Toxoplasma infection
慢性弓形虫感染中的新型液泡生物学
  • 批准号:
    10092083
  • 财政年份:
    2020
  • 资助金额:
    $ 22.24万
  • 项目类别:
Intravacuolar network dense granule protein biology in chronic Toxoplasma infection
慢性弓形虫感染中的液泡内网络致密颗粒蛋白生物学
  • 批准号:
    10010660
  • 财政年份:
    2020
  • 资助金额:
    $ 22.24万
  • 项目类别:
Dense granule protein virulence factors in Toxoplasma gondii infection
弓形虫感染中的致密颗粒蛋白毒力因子
  • 批准号:
    8730970
  • 财政年份:
    2014
  • 资助金额:
    $ 22.24万
  • 项目类别:
Parasite secreted proteins control host response to Toxoplasma gondii infection
寄生虫分泌的蛋白质控制宿主对弓形虫感染的反应
  • 批准号:
    8605518
  • 财政年份:
    2013
  • 资助金额:
    $ 22.24万
  • 项目类别:
Parasite secreted proteins control host response to Toxoplasma gondii infection
寄生虫分泌的蛋白质控制宿主对弓形虫感染的反应
  • 批准号:
    8466449
  • 财政年份:
    2013
  • 资助金额:
    $ 22.24万
  • 项目类别:
Toxoplasma gondii GRA protein function
弓形虫GRA蛋白功能
  • 批准号:
    8588116
  • 财政年份:
    2013
  • 资助金额:
    $ 22.24万
  • 项目类别:

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N-乙酰半乳糖胺-4-硫酸酯酶(芳基硫酸酯酶 B)对黑色素瘤进展的影响
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  • 批准号:
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    1991
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