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Research Interests
Toxoplasma gondii egress and invasion.
Research Summary
Toxoplasma gondii is an obligate intracellular parasite capable of infecting virtually any nucleated cell from a wide range of mammalian and avian species. Toxoplasma is one of the most widespread and successful protozoan pathogens and is a common parasite in humans where it has become one of the main opportunistic pathogens in AIDS patients. Moreover, in congenital infections, the disease can lead to severe neurological problems or even death of the developing fetus. Toxoplasmosis affects approximately one in every10,000 births in the United States. Because of its host broad range, Toxoplasma is also an important pathogen of animals. Toxoplasmosis is one of the principle causes of abortions in sheep and goats. In some sheep flocks it can be responsible for the deaths of half the newborns and thus it has devastating effects on this industry. Some of the most devastating effects of infections by intracellular parasites are a direct consequence of their lytic cycle, which consists of attachment to the host cell, invasion, intracellular replication and egress. Both invasion and egress by the human pathogen Toxoplasma gondii are essential for infection and survival, involve fluctuation in intracellular [Ca+2], morphological changes and secretion from various organelles. The goals of our lab are to answer the specific questions: "what are the molecular and genetic elements involved in egress?"; "what are the cues telling the parasite to exit its host cell?"; and "what are the molecular mechanisms involved in invasion?". To answer these questions, our lab utilizes a combination of molecular genetics, cell biology, and biochemistry. Infection of the fetus by Toxoplasma requires crossing of the placental barrier and thus, invasion and egress from various cell types. Consequently, inhibiting invasion or egress would stop the progress of congenital infection. A better understanding of the genes and events involved in the way the parasite invades and comes out of the host cell will shed light into its pathogenesis as well as reveal potential targets for drug and vaccine development.
Research Publications
Saeij, J., Arrizabalaga, G. and Boothroyd J.C., 2008. A cluster of four surface antigen genes specifically expressed in bradyzoites, SAG2CDXY, plays an important role in Toxoplasma gondii persistence. Immunity and infection, 76(6):2402-10
Lavine, M and Arrizabalaga, G., 2008 Exit from host cells by the pathogenic parasite Toxoplasma gondii does not require motility. Eukaryotic Cell, 7(1): 131-40 Lavine, M.D., Knoll, L.J., Rooney, P.J. and Arrizabalaga, G. 2007. A Toxoplasma gondii mutant defective in responding to calcium fluxes shows reduced in vivo pathogenicity. Molecular and Biochemical Parasitology, Molecular and Biochemical Parasitology, 155(2): 113-122 Fruth, I.A. and Arrizabalaga G., 2007. Toxoplasma gondii: Induction of egress by the potassium ionophore nigericin. International Journal of Parasitology, 37(14): 1559-67