title: Candida albicans Czf1 and Efg1 coordinate the response to farnesol during quorum sensing, white-opaque thermal dimorphism, and cell death.
abstract: Quorum sensing by farnesol in Candida albicans inhibits filamentation and may be directly related to its ability to cause both mucosal and systemic diseases. The Ras1-cyclic AMP signaling pathway is a target for farnesol inhibition. However, a clear understanding of the downstream effectors of the morphological farnesol response has yet to be unraveled. To address this issue, we screened a library for mutants that fail to respond to farnesol. Six mutants were identified, and the czf1Δ/czf1Δ mutant was selected for further characterization. Czf1 is a transcription factor that regulates filamentation in embedded agar and also white-to-opaque switching. We found that Czf1 is required for filament inhibition by farnesol under at least three distinct environmental conditions: on agar surfaces, in liquid medium, and when embedded in a semisolid agar matrix. Since Efg1 is a transcription factor of the Ras1-cyclic AMP signaling pathway that interacts with and regulates Czf1, an efg1Δ/efg1Δ czf1Δ/czf1Δ mutant was tested for filament inhibition by farnesol. It exhibited an opaque-cell-like temperature-dependent morphology, and it was killed by low farnesol levels that are sublethal to wild-type cells and both efg1Δ/efg1Δ and czf1Δ/czf1Δ single mutants. These results highlight a new role for Czf1 as a downstream effector of the morphological response to farnesol, and along with Efg1, Czf1 is involved in the control of farnesol-mediated cell death in C. albicans.
authors.affiliation: School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Langford
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Hargarten
authors.forename: Krista D
authors.initials: KD
authors.lastname: Patefield
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Marta
authors.forename: Jill R
authors.initials: JR
authors.lastname: Blankenship
authors.forename: Saranna
authors.initials: S
authors.lastname: Fanning
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Nickerson
authors.forename: Audrey L
authors.initials: AL
authors.lastname: Atkin
mesh_terms: D002176:Candida albicans / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005204:Farnesol / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D009154:Mutation; D053038:Quorum Sensing; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; D014157:Transcription Factors; C077336:CZF1 protein, Candida albicans; D005204:Farnesol