The long term objectives are to characterize the surface antigens expressed by Candida albicans during in vitro and in vivo development, determine if monoclonal antibodies raised against these antigens may be used to biotype strains of C. albicans, and extract and chemically characterize antigens which may be important in pathogenesis. The first objective will be done by establishing a bank of monoclonal antibodies specific for surface antigens of C. albicans and use these in conjunction with immunocolloidal gold electron microscopic techniques. The second objective will entail reacting the antibodies with many strains of the fungus grown under specified conditions. The third objective will be done by using mutants to identify pathogenetic determinants and monoclonal antibodies to purify the antigens from cell wall extracts. To induce antibody responses to many surface antigens, mice will be immunized to a variety of cell wall and other subcellular fractions. Some cell wall fractions will be enriched for hyphal- specific antigens. Specificities of monoclonal antibodies resulting from fusions of sensitized spleen cells with plasmacytoma cells will be determined by crossed immunoelectrophoretic techniques. The various antibodies will be used to detect antigen expression among many isolates of C. albicans and other yeasts to determine if the antibodies could be used for biotyping C. albicans strains. In addition, characterization of antigen expression on selected strains will be done by following yeast and hyphal development in vitro and in vivo at the level of electron microscopic analysis. These studies will provide comprehensive knowledge concerning the stability or variability of candidal antigen expression during development of cadidiasis in a murine model of this disease. A bank of monoclonal antibodies to the various antigens will be developed as a result of this work and these antibodies will be used to select mutants unable to produce a particular surface determinant. Virulence of these mutants will be tested in mouse models of candidiasis to ascertain which antigens may be related to the ability to cause disease. Such antigens will be isolated from wild type strains and chemically characterized.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI024912-02
Application #
3138174
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1988-03-01
Project End
1992-02-28
Budget Start
1989-03-01
Budget End
1990-02-28
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Montana State University Bozeman
Department
Type
Schools of Arts and Sciences
DUNS #
City
Bozeman
State
MT
Country
United States
Zip Code
59717
Cartmell, Jonathan; Paszkiewicz, Eugenia; Dziadek, Sebastian et al. (2015) Synthesis of antifungal vaccines by conjugation of ?-1,2 trimannosides with T-cell peptides and covalent anchoring of neoglycopeptide to tetanus toxoid. Carbohydr Res 403:123-34
Xin, Hong; Dziadek, Sebastian; Bundle, David R et al. (2008) Synthetic glycopeptide vaccines combining beta-mannan and peptide epitopes induce protection against candidiasis. Proc Natl Acad Sci U S A 105:13526-31
Xin, Hong; Cutler, Jim E (2006) Hybridoma passage in vitro may result in reduced ability of antimannan antibody to protect against disseminated candidiasis. Infect Immun 74:4310-21
Mochon, A Brian; Cutler, Jim E (2005) Is a vaccine needed against Candida albicans? Med Mycol 43:97-115
Granger, Bruce L; Flenniken, Michelle L; Davis, Dana A et al. (2005) Yeast wall protein 1 of Candida albicans. Microbiology 151:1631-44
Cutler, J E (2005) Defining criteria for anti-mannan antibodies to protect against candidiasis. Curr Mol Med 5:383-92
Wang, Ping; Cutler, Jim; King, Jill et al. (2004) Mutation of the regulator of G protein signaling Crg1 increases virulence in Cryptococcus neoformans. Eukaryot Cell 3:1028-35
Montagnoli, Claudia; Bozza, Silvia; Bacci, Angela et al. (2003) A role for antibodies in the generation of memory antifungal immunity. Eur J Immunol 33:1193-204
Kruppa, Michael; Goins, Tresa; Cutler, Jim E et al. (2003) The role of the Candida albicans histidine kinase [CHK1) gene in the regulation of cell wall mannan and glucan biosynthesis. FEMS Yeast Res 3:289-99
Sundstrom, Paula; Cutler, Jim E; Staab, Janet F (2002) Reevaluation of the role of HWP1 in systemic candidiasis by use of Candida albicans strains with selectable marker URA3 targeted to the ENO1 locus. Infect Immun 70:3281-3

Showing the most recent 10 out of 46 publications