title: Developmental regulation of an adhesin gene during cellular morphogenesis in the fungal pathogen Candida albicans.
abstract: Candida albicans expresses specific virulence traits that promote disease establishment and progression. These traits include morphological transitions between yeast and hyphal growth forms that are thought to contribute to dissemination and invasion and cell surface adhesins that promote attachment to the host. Here, we describe the regulation of the adhesin gene ALS3, which is expressed specifically during hyphal development in C. albicans. Using a combination of reporter constructs and regulatory mutants, we show that this regulation is mediated by multiple factors at the transcriptional level. The analysis of ALS3 promoter deletions revealed that this promoter contains two activation regions: one is essential for activation during hyphal development, while the second increases the amplitude of this activation. Further deletion analyses using the Renilla reniformis luciferase reporter delineate the essential activation region between positions -471 and -321 of the promoter. Further 5' or 3' deletions block activation. ALS3 transcription is repressed mainly by Nrg1 and Tup1, but Rfg1 contributes to this repression. Efg1, Tec1, and Bcr1 are essential for the transcriptional activation of ALS3, with Tec1 mediating its effects indirectly through Bcr1 rather than through the putative Tec1 sites in the ALS3 promoter. ALS3 transcription is not affected by Cph2, but Cph1 contributes to full ALS3 activation. The data suggest that multiple morphogenetic signaling pathways operate through the promoter of this adhesin gene to mediate its developmental regulation in this major fungal pathogen.
authors.affiliation: School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Silvia
authors.initials: S
authors.lastname: Argimón
authors.forename: Jill A
authors.initials: JA
authors.lastname: Wishart
authors.forename: Roger
authors.initials: R
authors.lastname: Leng
authors.forename: Susan
authors.initials: S
authors.lastname: Macaskill
authors.forename: Abigail
authors.initials: A
authors.lastname: Mavor
authors.forename: Thomas
authors.initials: T
authors.lastname: Alexandris
authors.forename: Susan
authors.initials: S
authors.lastname: Nicholls
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Knight
authors.forename: Brice
authors.initials: B
authors.lastname: Enjalbert
authors.forename: Richard
authors.initials: R
authors.lastname: Walmsley
authors.forename: Frank C
authors.initials: FC
authors.lastname: Odds
authors.forename: Neil A R
authors.initials: NA
authors.lastname: Gow
authors.forename: Alistair J P
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D002176:Candida albicans / Q000166:cytology / Q000235:genetics* / Q000254:growth & development*; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015966:Gene Expression Regulation, Fungal; D025301:Hyphae / Q000254:growth & development; D007700:Kinetics; D008957:Models, Genetic; D009024:Morphogenesis; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; C489432:TEC1 protein, Candida albicans; D014157:Transcription Factors