: This is a revised proposal (R01AI150471-01) in response to PA 99-124. The goal of this project is a comprehensive characterization of Cryptosporidium parvum type 1, the most common agent of human cryptosporidiosis in the general population and in people with AIDS. Because until recently type 1 C. parvum could not be propagated in the laboratory, this subgroup is rarely studied and remains poorly characterized. As a consequence, phenotypic properties of calf-propagated type 2 oocysts are extrapolated to the whole species. In light of the significant public health importance of cryptosporidiosis caused by type 1 C. parvum, the emphasis of this proposal is twofold: 1) to extensively characterize C. parvum type 1 with respect to genotypic and phenotypic properties, as well as its life cycle and interaction with the host, and (2) to compare C. parvum type 1 and type 2 with the aim of gaining a better understanding of the species C. parvum and the disease caused by this parasite. The recent development of a gnotobiotic pig model suitable for propagation of type 1 and type 2 will facilitate the study of several type 1 isolates and the comparison of standardized C. parvum isolates of both types originating from the same host. The interaction of type 1 and type 2 isolates in mixed infections will also be studied in the pig model. Type 1 isolates included in this study will originate from chronic and acute infections and from different geographical areas. The study includes three specific aims:
the first aim i s a comprehensive analysis of ten type 1 C. parvum isolates. In the second aim the host-parasite interaction of type 1 and type 2 isolates will be compared using the pig model and cell culture models.
The third aim i nvestigates the extent of genetic variation and exchange within and between the two types of C. parvum to determine whether they belong to one or two species.
