POTASSIUM SENSING BY THE OBLIGATE INTRACELLULAR PARASITE TOXOPLASMA GONDII

专性细胞内寄生虫弓形虫的钾感应

• 批准号: 7720364
• 负责人: Gustavo A Arrizabalaga
• 金额: $ 18.49万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720364
• 关键词: Acquired Immunodeficiency Syndrome; Apicomplexa; Calcium; Cells; Cessation of life; Coccidiosis; Communication; Computer Retrieval of Information on Scientific Projects Database; Cues; DNA Sequence Rearrangement; Disease; Environment; Event; Funding; Genes; Goals; Grant; Immunocompromised Host; Individual; Infection; Infectious Agent; Institution; Lead; Light; Lytic Phase; Malaria; Malignant Neoplasms; Modification; Molecular Analysis; Molecular Genetics; Organism; Potassium; Research; Research Personnel; Resources; Signal Transduction; Source; Toxoplasma; Toxoplasma gondii; United States National Institutes of Health; in utero; member; mutant; obligate intracellular parasite; pathogen

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The obligate intracellular infectious agent Toxoplasma gondii is a member of the phylum Apicomplexa, which includes the organisms responsible for malaria and coccidiosis. Although most Toxoplasma infections are asymptomatic, they can lead to severe disease and even death in utero and in individuals immunocompromised by AIDS or cancer. Some of the devastating effects of a Toxoplasma infection are a direct consequence of its lytic cycle, which consists of attachment to the host cell, invasion, intracellular replication and egress. Both invasion and egress involve fluctuation in intracellular calcium concentration, morphological rearrangements and modifications to the host cell. The specific genes and cues involved in these rapid and active events are not known. It has been observed, however, that a decrease in potassium concentration within the host cell can serve as a signal for Toxoplasma egress. It is the goal of this proposal to elucidate the unknown genetic and molecular mechanisms utilized by this pathogen to sense changes in the environment as it specifically regards to potassium fluxes. This will be accomplished by isolating and characterizing mutants with an altered sensitivity to potassium concentration changes. The phenotypic and molecular analysis of these mutants will identify the genes involved in perceiving the pivotal changes in potassium concentration important during egress as well shed light to events critical to host-pathogen communication.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 专性细胞内传染原弓形虫是顶复门的成员，该门包括导致疟疾和球虫病的生物体。 尽管大多数弓形虫感染是无症状的，但它们可以在子宫内以及因艾滋病或癌症而免疫功能低下的个体中导致严重疾病甚至死亡。 弓形虫感染的一些破坏性影响是其裂解周期的直接后果，该裂解周期包括附着于宿主细胞、入侵、细胞内复制和流出。 入侵和流出都涉及细胞内钙浓度的波动、形态重排和宿主细胞的修饰。 这些快速而活跃的事件所涉及的具体基因和线索尚不清楚。 然而，据观察，宿主细胞内钾浓度的降低可以作为弓形虫流出的信号。 该提案的目的是阐明该病原体利用未知的遗传和分子机制来感知环境的变化，因为它特别涉及钾通量。 这将通过分离和表征对钾浓度变化敏感性改变的突变体来实现。 这些突变体的表型和分子分析将鉴定参与感知钾浓度关键变化的基因，这些变化在逃逸过程中很重要，并揭示对宿主-病原体通讯至关重要的事件。