The Ess1 prolyl isomerase is required for growth and morphogenetic switching in Candida albicans.
Prolyl-isomerases (PPIases) are found in all organisms and are important for the folding and activity of many proteins. Of the 13 PPIases in Saccharomyces cerevisiae only Ess1, a parvulin-class PPIase, is essential for growth. Ess1 is required to complete mitosis, and Ess1 and its mammalian homolog, Pin1, interact directly with RNA polymerase II. Here, we isolate the ESS1 gene from the pathogenic fungus Candida albicans and show that it is functionally homologous to the S. cerevisiae ESS1. We generate conditional-lethal (ts) alleles of C. albicans ESS1 and use these mutations to demonstrate that ESS1 is essential for growth in C. albicans. We also show that reducing the dosage or activity of ESS1 blocks morphogenetic switching from the yeast to the hyphal and pseudohyphal forms under certain conditions. Analysis of double mutants of ESS1 and TUP1 or CPH1, two genes known to be involved in morphogenetic switching, suggests that ESS1 functions in the same pathway as CPH1 and upstream of or in parallel to TUP1. Given that switching is important for virulence of C. albicans, inhibitors of Ess1 might be useful as antifungal agents.
Devasahayam
Gina
G
Molecular Genetics Program, Wadsworth Center, New York State Department of Health, Albany, New York 12208, USA.
Chaturvedi
Vishnu
V
Hanes
Steven D
SD
D000595:Amino Acid Sequence; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D020043:Genes, Essential; D005800:Genes, Fungal; D005812:Genes, Switch; D006801:Humans; D025301:Hyphae / Q000254:growth & development; D008969:Molecular Sequence Data; D009154:Mutation; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000254:growth & development; D017386:Sequence Homology, Amino Acid
D005656:Fungal Proteins; D019696:Peptidylprolyl Isomerase