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An Investigation of Potassium sensing by the obligate intracellular parasite
Toxoplasma gondii |
Co-P.I. Gustavo Arrizabalaga
Abstract |
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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 [Ca+2], 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 [K+] within the host cell serves 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 within its host as it specifically regards to K+ fluxes. This will be accomplished by
isolating and characterizing mutants with an altered sensitivity to [K+] changes. The genetic scheme designed for this purpose
takes advantage that changes in [K+] outside the parasites also influences invasion which is reversibly inhibited in a high
[K+] buffer. Accordingly, mutant parasites resistant to this invasion block and also those unable to recover from it will be
isolated through a series of genetic selections and screens. The phenotypic and molecular analysis of these mutants will
identify the genes involved in perceiving the pivotal changes in [K+] important during egress and invasion as well shed light
to events critical to host-pathogen communication.
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| researchers |
| Gustavo Arrizabalaga |
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| Potassium sensing by the obligate intracellular parasite Toxoplasma gondii |
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