Affiliation:
1. Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455
Abstract
ABSTRACT
The success of
Candida albicans
as a major human fungal pathogen is dependent on its ability to colonize and survive as a commensal on diverse mucosal surfaces. One trait required for survival and virulence in the host is the morphogenetic yeast-to-hypha transition. Mds3 was identified as a regulator of pH-dependent morphogenesis that functions in parallel with the classic Rim101 pH-sensing pathway. Microarray analyses revealed that
mds3
Δ/Δ cells had an expression profile indicative of a hyperactive TOR pathway, including the preferential expression of genes encoding ribosomal proteins and a decreased expression of genes involved in nitrogen source utilization. The transcriptional and morphological defects of the
mds3
Δ/Δ mutant were rescued by rapamycin, an inhibitor of TOR, and this rescue was lost in strains carrying the rapamycin-resistant
TOR1
-
1
allele or an
rbp1
Δ/Δ deletion. Rapamycin also rescued the transcriptional and morphological defects associated with the loss of Sit4, a TOR pathway effector, but not the loss of Rim101 or Ras1. The
sit4
Δ/Δ and
mds3
Δ/Δ mutants had additional phenotypic similarities, suggesting that Sit4 and Mds3 function similarly in the TOR pathway. Finally, we found that Mds3 and Sit4 coimmunoprecipitate. Thus, Mds3 is a new member of the TOR pathway that contributes to morphogenesis in
C. albicans
as a regulator of this key morphogenetic pathway.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
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