title: Dominant active alleles of RIM101 (PRR2) bypass the pH restriction on filamentation of Candida albicans.
abstract: Morphological development of the fungal pathogen Candida albicans is profoundly affected by ambient pH. Acidic pH restricts growth to the yeast form, whereas neutral pH permits development of the filamentous form. Superimposed on the pH restriction is a temperature requirement of approximately 37 degrees C for filamentation. The role of pH in development was investigated by selecting revertants of phr2Delta mutants that had gained the ability to grow at acid pH. The extragenic suppressors in two independent revertants were identified as nonsense mutations in the pH response regulator RIM101 (PRR2) that resulted in a carboxy-terminal truncation of the open reading frame. These dominant active alleles conferred the ability to filament at acidic pH, to express PHR1, an alkaline-expressed gene, at acidic pH, and to repress the acid-expressed gene PHR2. It was also observed that both the wild-type and mutant alleles could act as multicopy suppressors of the temperature restriction on filamentation, allowing extensive filamentation at 29 degrees C. The ability of the activated alleles to promote filamentation was dependent upon the developmental regulator EFG1. The results suggest that RIM101 is responsible for the pH dependence of hyphal development.
authors.affiliation: Institut für Hygiene und Mikrobiologie, Universität Würzburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: El Barkani
authors.forename: O
authors.initials: O
authors.lastname: Kurzai
authors.forename: W A
authors.initials: WA
authors.lastname: Fonzi
authors.forename: A
authors.initials: A
authors.lastname: Ramon
authors.forename: A
authors.initials: A
authors.lastname: Porta
authors.forename: M
authors.initials: M
authors.lastname: Frosch
authors.forename: F A
authors.initials: FA
authors.lastname: Mühlschlegel
mesh_terms: D001051:Apoenzymes / Q000235:genetics / Q000378:metabolism; D002176:Candida albicans / Q000502:physiology*; D002455:Cell Division / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage; D015966:Gene Expression Regulation, Fungal; D005799:Genes, Dominant; D006579:Heterozygote; D006863:Hydrogen-Ion Concentration; D008562:Membrane Glycoproteins; D009154:Mutation; D013489:Suppression, Genetic; D014157:Transcription Factors
chemical_list: D001051:Apoenzymes; D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; C091515:PHR1 protein, Candida albicans; C489602:RIM101 protein, Candida albicans; D014157:Transcription Factors; D004255:Deoxyribodipyrimidine Photo-Lyase