In immuocompromised patients, latent infection with the obligate

intracellular parasite Toxoplasma gondii often recrudesces in the central

nervous system to produce the most severe manifestations of toxoplasmosis,

Toxoplasmic encephalitis.  Hallmark features of Toxoplasmic encephalitis

are large necrotic lesions visible by computerized tomography (CT) or magnetic

resonance (MR) imaging of the brain.  Although the basis of this pathology in

vivo is incompleteley understood, it is likely directly the result of

Toxoplasma’s astonishing propensity to destroy host cells through its lytic

cycle.  The Toxoplasma lytic cycle has three main steps: invasion,

replication and egress.  Our studies focus on elucidating the mechanism of

toxoplasma invasion, with the premise that identification of the key invasion

proteins will lead to their exploitation as targets for drug or vaccine

development.  We have demonstrated that invasion proteins are mobilized

from intracellular secretory vesicles (micronemes) concomitant with parasite

attachment to host cells.  Also, we determined that some of the invasion

proteins are adhesions capable of binding receptors on host cells. 

Furthermore, we showed that one host cell receptor Toxoplasma use for attachment

are common cell surface glycoproteins, known as heparan sulfate proteoglycans. 

By demonstrating that Toxoplasma uses multiple adhesions and ubiquitously

expressed receptors, these studies have revealed the molecular basis for

Toxoplasma’s ability to infect a variety of cells and tissues within its many

vertebrate hosts.