title: Mds3 regulates morphogenesis in Candida albicans through the TOR pathway.
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 Delta/Delta 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 Delta/Delta 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 Delta/Delta 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 Delta/Delta and mds3 Delta/Delta 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.
authors.affiliation: Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Lucia F
authors.initials: LF
authors.lastname: Zacchi
authors.forename: Jonatan
authors.initials: J
authors.lastname: Gomez-Raja
authors.forename: Dana A
authors.initials: DA
authors.lastname: Davis
mesh_terms: D001483:Base Sequence; D002176:Candida albicans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism* / Q000472:pathogenicity; D017931:DNA Primers / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal; D006801:Humans; D009024:Morphogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D004271:DNA, Fungal; D005656:Fungal Proteins; D020123:Sirolimus
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