Candida albicans is an opportunistic dimorphic fungus capable of causing devastating disease in humans. Recent observations have suggested that the surface topography of the cell is dynamic rather than static and variable expression of surface components may occur not just on cells grown under different conditions but on single cells during their lifetime. Such dynamics reflect on mechanisms of synthesis of the cell wall components and their assembly into a functional structure and suggest an additional hierarchy of regulation. They also impact on the commensal and pathogenic relationship of the organism and the host as the organism colonizes the normal host and escapes normal defenses to establish infection in the compromised host. This proposal focuses on the mannoproteins which are the least studied of the wall constituents and have potential for greatest sequence diversity. Mannoprotein has been shown to be at the surface of the cell and both mannan and protein have been implicated in adherence of the fungus to tissue. The research will take the approach of producing monoclonal antibodies to both car bohydrate and protein portions of mannoproteins to identify surface components. The reactivity of these antibodies will be determined with whole cells using indirect immunofluorescence. The nature and identity of the antigenic determinant will be examined using immunoblotting techniques, sensitivity of the antigen to various reagents and other techniques. The extent of epitope expression by growing and stationary phase yeasts cultivated at 28 degrees C and 37 degrees C and germ tubes cultivated at 37 degrees C will be determined. The patterns of expression, kinetics of changes in expression and nature of the determinant will be examined for patterns to develop hypotheses for the regulation of expression and the mechanisms by which such changes are effected. The ability of antibodies to react with surface components will be exploited in studying host-parasite interactions in adherence of fungi to human epithelial cells. Such antibodies will be utilized to select for mutants altered in expression of surface epitopes and these mutants characterized for surface expression and tissue adherence.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI023416-01
Application #
3135467
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Texas Tech University
Department
Type
Schools of Medicine
DUNS #
609980727
City
Lubbock
State
TX
Country
United States
Zip Code
79430
Vediyappan, G; Bikandi, J; Braley, R et al. (2000) Cell surface proteins of Candida albicans: preparation of extracts and improved detection of proteins. Electrophoresis 21:956-61
Lopez-Ribot, J L; Bikandi, J; San Millan, R S et al. (1999) Interactions between Candida albicans and the human extracellular matrix component tenascin-C. Mol Cell Biol Res Commun 2:58-63
Braley, R; Chaffin, W L (1999) Variations in mRNA transcript levels of cell wall-associated genes of Saccharomyces cerevisiae following spheroplasting. FEMS Microbiol Lett 181:177-85
Cannon, R D; Chaffin, W L (1999) Oral colonization by Candida albicans. Crit Rev Oral Biol Med 10:359-83
Martinez, J P; Gil, M L; Lopez-Ribot, J L et al. (1998) Serologic response to cell wall mannoproteins and proteins of Candida albicans. Clin Microbiol Rev 11:121-41
Chaffin, W L; Lopez-Ribot, J L; Casanova, M et al. (1998) Cell wall and secreted proteins of Candida albicans: identification, function, and expression. Microbiol Mol Biol Rev 62:130-80
Alloush, H M; Lopez-Ribot, J L; Masten, B J et al. (1997) 3-phosphoglycerate kinase: a glycolytic enzyme protein present in the cell wall of Candida albicans. Microbiology 143 ( Pt 2):321-30
Sepulveda, P; Lopez-Ribot, J L; Gozalbo, D et al. (1996) Ubiquitin-like epitopes associated with Candida albicans cell surface receptors. Infect Immun 64:4406-8
Lopez-Ribot, J L; Alloush, H M; Masten, B J et al. (1996) Evidence for presence in the cell wall of Candida albicans of a protein related to the hsp70 family. Infect Immun 64:3333-40
Alloush, H M; Lopez-Ribot, J L; Chaffin, W L (1996) Dynamic expression of cell wall proteins of Candida albicans revealed by probes from cDNA clones. J Med Vet Mycol 34:91-7

Showing the most recent 10 out of 29 publications