Two waterborne apicomplexan protozoa, Toxoplasma
gondii and Cryptosporidium parvum, are potential biological weapons. T. gondii,
a ubiquitous parasite of mammals and birds, has long been recognized as an important
pathogen of both immune competent and immunocompromised hosts. T.gondii
infection during pregnancy can result in congenital toxoplasmosis with associated
encephalitis and chorioretinitis. In addition to its effects on children, adults
can become infected with T. gondii through water supplies or food. The major syndrome
caused by C. parvum is diarrhea, which can last for several weeks and can cause
dehydration and death. Like T. gondii, the oocysts of this organism are also
environmentally resistant and water-borne outbreaks have been described.
The apicomplexan cytoskeletal scaffold is a primary
determinant of cell shape, and tethers functional protein assemblies in the cytosol
and overlying membranes. Membrane proteins are positioned at the contact interface of
parasites and their hosts and are involved in a diverse range of cellular functions
including cell signaling/communication, nutrient and ion transport. We will use
proteomics approaches to identify the proteins mediating inter- and intramolecular
associations within the cytoskeletal complex as well as the overlying membranes.
These macromolecular assemblies and membrane protein complexes, given their importance
for cell function, will provide a rich source of novel targets for chemotherapy.