Essential GPI Mannosyltransferases in Saccharomyces Cerevisiae and the Pathogenic Fungus Candida Albicans
Grimme, Stephen James
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/84804
Description
Title
Essential GPI Mannosyltransferases in Saccharomyces Cerevisiae and the Pathogenic Fungus Candida Albicans
Author(s)
Grimme, Stephen James
Issue Date
2004
Doctoral Committee Chair(s)
Peter A.B.Orlean
Department of Study
Biochemistry
Discipline
Biochemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Cell
Language
eng
Abstract
I cloned the C. albicans homologue of SMP3 and found that its product is the functional homologue of ScSmp3p, for it complements null and conditional smp3 mutations. Furthermore, CaSmp3p transfers a fourth mannose to a trimannosyl-GPI precursor in vivo. I determined that CaSMP3 is also an essential gene, as I was unable to recover homozygous null smp3 mutants from C. albicans, an obligate diploid. I created a conditional strain in which expression of CaSMP3 was controlled by the CaMAL2 promoter, and found that depletion of CaSmp3p results in the accumulation of a trimannosyl-GPI precursor and decreased viability. My characterization of this precursor is the first report of a GPI structure from C. albicans . The MAL2 promoter offers a tool to perform functional analysis studies on other C. albicans GPI assembly genes. Several C. albicans GPI anchored proteins have been implicated in virulence and disruption of GPI biosynthesis should globally impair the surface expression of these proteins. Because Smp3p is essential in fungi, yet dispensable in mammalian cells, its function could be exploited as a target for selective inhibitors of pathogenic fungi.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.