The Glyoxylate Cycle Is Involved in White-Opaque Switching in Candida albicans

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 (WOR1(OE)) suggested an altered metabolism of carbon sources and a phenotypic analysis confirmed this alteration. The WOR1(OE) 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 icl1 Delta/Delta 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 mtla1 Delta icl1 Delta/Delta cells, suggesting the involvement of Icl1 in the adaptation to the commensal state. In fact, icl1 Delta/Delta cells have reduced fitness in mouse gastrointestinal tract as compared with essentially isogenic heterozygous ICL1/icl1 Delta, but overproduction of WOR1 in an icl1 Delta/Delta 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.

Automated summary

The study reveals that the isocitrate lyase enzyme Icl1 plays a crucial role in the adaptation of Candida albicans to a commensal state, as mutants lacking Icl1 show reduced fitness in the mouse gastrointestinal tract.