The immunology and immunochemistry of two parasites that cause considerable disease in the United States are studied. Giardia lamblia is the most common disease-causing parasite in the United States. Giardia undergoes surface antigenic variation where the parasite?s surface changes periodically. These surface proteins are important because it allows the parasite to survive in the intestine where the parasite multiplies and is a target of the host?s immune system. Antibodies to the surface antigen kill the parasite so that knowing what portions of the surface antigens are targets of the host response and what parts of the protein are essential to the parasite can led to ways to prevent or cure infections. Using newly developed methods to put genes into Giardia , we studied what regions of a specific surface protein are important in making these proteins and placing them on the surface of the parasite. By destroying several conserved features common to these proteins( called motifs) we showed that altering the GGCY motif, the conserved lipid-like tail of the protein and a part that binds Zn were essential to make a protein that could be placed onto the surface of the parasite. The second group of parasites studied is microsporidia, which is group of related parasites that cause diarrhea and sometimes systemic infections in AIDS patients. We are interested in the identification and characterization of parasite proteins that are important for survival of the parasite in the host and host proteins that are called into play when the parasite invades the cell. A number of proteins have been identified. However, the most important and perhaps useful is the identification and characterization of 2 spore wall proteins in one important species, Encephalitozoon. intestinalis. The first protein is made by the developing parasite just when it begins to form the spore wall. The second spore wall protein is present mostly in the mature spore. By an as yet unknown mechanisms the two spore wall proteins are joined together, processed and sugar molecules added to them. Understanding how the spore wall forms is important because it allows the parasite to survive outside the host and interrupting the process might lead to both treatment and prevention of infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000161-24
Application #
6506771
Study Section
(LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
24
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Kulakova, Liudmila; Singer, Steven M; Conrad, John et al. (2006) Epigenetic mechanisms are involved in the control of Giardia lamblia antigenic variation. Mol Microbiol 61:1533-42
Hayman, J Russell; Southern, Timothy R; Nash, Theodore E (2005) Role of sulfated glycans in adherence of the microsporidian Encephalitozoon intestinalis to host cells in vitro. Infect Immun 73:841-8
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Davis-Hayman, Sara R; Hayman, J Russell; Nash, Theodore E (2003) Encystation-specific regulation of the cyst wall protein 2 gene in Giardia lamblia by multiple cis-acting elements. Int J Parasitol 33:1005-12
Touz, Maria C; Nores, Maria J; Slavin, Ileana et al. (2002) The activity of a developmentally regulated cysteine proteinase is required for cyst wall formation in the primitive eukaryote Giardia lamblia. J Biol Chem 277:8474-81

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