Abstract
Candida albicans is a commensal yeast that inhabits the gastrointestinal tract of humans. The master regulator of the white-opaque transition WOR1 has been implicated in the adaptation to this commensal status. A proteomic analysis of cells overexpressing this transcription factor (WOR1OE) suggested an altered metabolism of carbon sources and a phenotypic analysis confirmed this alteration. The WOR1OE cells are deficient in using trehalose and xylose and are unable to use 2C sources, which is consistent with a reduction in the amount of Icl1, the isocitrate lyase enzyme. The icl1Δ/Δ mutants overexpressing WOR1 are deficient in the production of phloxine B positive cells, a main characteristic of opaque cells, a phenotype also observed in mating type hemizygous mtla1Δ icl1Δ/Δ cells, suggesting the involvement of Icl1 in the adaptation to the commensal state. In fact, icl1Δ/Δ cells have reduced fitness in mouse gastrointestinal tract as compared with essentially isogenic heterozygous ICL1/icl1Δ, but overproduction of WOR1 in an icl1Δ/Δ mutant does not restore fitness. These results implicate the glyoxylate shunt in the adaptation to commensalism of C. albicans by mechanisms that are partially independent of WOR1.
Highlights
Candida albicans is a commensal yeast that inhabits the gastrointestinal tract of healthy people, where it behaves as a harmless commensal
We demonstrate that the growth of WOR1 overexpression (WOR1OE) cells is altered in the presence of alternative carbon sources and show a role for the glyoxylate cycle in the production of opaque cells and the fitness of C. albicans cells in mouse GI tract
Empty control vector pNRUe [40] and pNRUX-WOR1-myc [38] tetracycline repressible plasmids that carry the URA3 marker were digested with KpnI and KspI and products were integrated at the ADH1 region of the MLC9 strain to generate icl1∆/∆pNRUe and icl1∆/∆-WOR1OE strains
Summary
Candida albicans is a commensal yeast that inhabits the gastrointestinal tract of healthy people, where it behaves as a harmless commensal. Other wo regulators have been identified among previously identified opaque-enriched genes [22,23] by in silico selection of transcriptional regulators [30] and the regulatory interactions among them analyzed by chromatin immunoprecipitation and gene expression profiling [30,31] or by a systematic screening using a collection of strains deleted for transcription factors [32] The complexity of this transition is revealed by the involvement of chromatin reorganization via histone modifications [33,34,35]. Wor has been suggested to mediate a morphological switch (termed GUT from gastrointestinally induced transition) via its increased expression upon passage through the mouse intestine, presumably converting a subset of C. albicans cells to the commensal status. We demonstrate that the growth of WOR1OE cells is altered in the presence of alternative carbon sources and show a role for the glyoxylate cycle in the production of opaque cells and the fitness of C. albicans cells in mouse GI tract
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