title: Role of Ess1 in growth, morphogenetic switching, and RNA polymerase II transcription in Candida albicans.
abstract: Candida albicans is a fungal pathogen that causes potentially fatal infections among immune-compromised individuals. The emergence of drug resistant C. albicans strains makes it important to identify new antifungal drug targets. Among potential targets are enzymes known as peptidyl-prolyl cis/trans isomerases (PPIases) that catalyze isomerization of peptide bonds preceding proline. We are investigating a PPIase called Ess1, which is conserved in all major human pathogenic fungi. Previously, we reported that C. albicans Ess1 is essential for growth and morphogenetic switching. In the present study, we re-evaluated these findings using more rigorous genetic analyses, including the use of additional CaESS1 mutant alleles, distinct marker genes, and the engineering of suitably-matched isogenic control strains. The results confirm that CaEss1 is essential for growth in C. albicans, but show that reduction of CaESS1 gene dosage by half (δ/+) does not interfere with morphogenetic switching. However, further reduction of CaEss1 levels using a conditional allele does reduce morphogenetic switching. We also examine the role of the linker α-helix that distinguishes C. albicans Ess1 from the human Pin1 enzyme, and present results of a genome-wide transcriptome analysis. The latter analysis indicates that CaEss1 has a conserved role in regulation of RNA polymerase II function, and is required for efficient termination of small nucleolar RNAs and repression of cryptic transcription in C. albicans.
authors.affiliation: Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, New York, United States of America.
authors.forename: Dhanushki
authors.initials: D
authors.lastname: Samaranayake
authors.forename: David
authors.initials: D
authors.lastname: Atencio
authors.forename: Randall
authors.initials: R
authors.lastname: Morse
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Wade
authors.forename: Vishnu
authors.initials: V
authors.lastname: Chaturvedi
authors.forename: Steven D
authors.initials: SD
authors.lastname: Hanes
mesh_terms: D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics*
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D012319:RNA Polymerase II; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase