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The apicomplexan Cryptosporidium parvum is an intestinal parasite that affects healthy humans and animals, and causes an unrelenting infection in immunocompromised individuals such as AIDS patients. We report the complete genome sequence of C. parvum, type II isolate. Genome analysis identifies extremely streamlined metabolic pathways and a reliance on the host for nutrients. In contrast to Plasmodium and Toxoplasma, the parasite lacks an apicoplast and its genome, and possesses a degenerate mitochondrion that has lost its genome. Several novel classes of cell-surface and secreted proteins with a potential role in host interactions and pathogenesis were also detected. Elucidation of the core metabolism, including enzymes with high similarities to bacterial and plant counterparts, opens new avenues for drug development.
Cryptosporidium parvum is a globally important intracellular pathogen of humans and animals. The duration of infection and pathogenesis of cryptosporidiosis depends on host immune status, ranging from a severe but self-limiting diarrhea in immunocompetent individuals to a life-threatening, prolonged infection in immunocompromised patients. A substantial degree of morbidity and mortality is associated with infections in AIDS patients. Despite intensive efforts over the past 20 years, there is currently no effective therapy for treating or preventing C. parvum infection in humans.
Cryptosporidium belongs to the phylum Apicomplexa, whose members share a common apical secretory apparatus mediating locomotion and tissue or cellular invasion. Many apicomplexans are of medical or veterinary importance, including Plasmodium, Babesia, Toxoplasma, Neosprora, Sarcocystis, Cyclospora, and Eimeria. The life cycle of C. parvum is similar to that of other cystforming apicomplexans (e.g., Eimeria and Toxoplasma), resulting in the formation of oocysts that are shed in the feces of infected hosts. C. parvum oocysts are highly resistant to environmental stresses, including chlorine treatment of community water supplies; hence, the parasite is an important water- and food-borne pathogen (1). The obligate inrracellular nature of the parasite's life cycle and the inability to culture the parasite continuously in vitro greatly impair researchers' ability to obtain purified samples of the different developmental stages. The parasite cannot be genetically manipulated, and transformation methodologies are currently unavailable. To begin to address these limitations, we have obtained the complete C. parvum genome sequence and its predicted protein complement. (This whole-genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the project accession AAEE00000000....