POTASSIUM SENSING BY OBLIGATE INTRACELLULAR PARASITE TOXOPLASMA GONDII: AIDS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。弓形虫是弓形虫的专性细胞内感染物，属于尖端复合门，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，但它们可能会导致严重的疾病，甚至在子宫内以及因艾滋病或癌症而免疫受损的人中死亡。弓形虫感染的一些破坏性影响是其溶解周期的直接结果，该周期包括对宿主细胞的附着、入侵、细胞内复制和出口。侵袭和外泄都涉及细胞内钙离子浓度的波动、形态重排和对宿主细胞的修饰。这些快速而活跃的事件中涉及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下降可以作为弓形虫出口的信号。这项建议的目的是阐明这种病原体用来感知环境变化的未知的遗传和分子机制，因为它特别与钾的通量有关。这将通过分离和鉴定对钾浓度变化敏感的突变株来实现。对这些突变体的表型和分子分析将确定与感知钾浓度的关键变化有关的基因，这些变化在出口过程中非常重要，并揭示了对宿主-病原体交流至关重要的事件。

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.