POTASSIUM SENSING BY THE OBLIGATE INTRACELLULAR PARASITE TOXOPLASMA GONDII

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 专性细胞内感染性病原体刚地弓形虫是顶复门的成员，该门包括引起疟疾和球虫病的生物体。 虽然大多数弓形虫感染是无症状的，但它们可导致严重的疾病，甚至在子宫内和因艾滋病或癌症而免疫功能低下的个体中死亡。 弓形虫感染的一些破坏性影响是其裂解周期的直接结果，其裂解周期包括附着于宿主细胞、侵入、细胞内复制和排出。 侵入和排出都涉及细胞内钙离子浓度的波动、形态学重排和对宿主细胞的修饰。 参与这些快速和活跃事件的特定基因和线索尚不清楚。 然而，已经观察到，宿主细胞内钾浓度的降低可以作为弓形虫排出的信号。 这是该提案的目标，以阐明未知的遗传和分子机制，利用这种病原体来感知环境中的变化，因为它特别是关于钾通量。 这将通过分离和表征对钾浓度变化具有改变的敏感性的突变体来实现。 对这些突变体的表型和分子分析将确定参与感知钾浓度关键变化的基因，这些变化在外出过程中很重要，也揭示了对宿主-病原体通信至关重要的事件。

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.