Essential GPI Mannosyltransferases in Saccharomyces Cerevisiae and the Pathogenic Fungus Candida Albicans

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Grimme, Stephen James

Contributors dc:contributor

• Peter A.B.Orlean

• Biology, Cell

Language dc:language

eng

Identifier

(MiAaPQ)AAI3130926

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84804