Candida albicansCzf1 and Efg1 Coordinate the Response to Farnesol during Quorum Sensing, White-Opaque Thermal Dimorphism, and Cell Death
Autor: | Langford, Melanie L., Hargarten, Jessica C., Patefield, Krista D., Marta, Elizabeth, Blankenship, Jill R., Fanning, Saranna, Nickerson, Kenneth W., Atkin, Audrey L. |
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Zdroj: | Eukaryotic Cell; July 2013, Vol. 12 Issue: 9 p1281-1292, 12p |
Abstrakt: | ABSTRACTQuorum sensing by farnesol in Candida albicansinhibits 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 czf1?/czf1? 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 efg1?/efg1? czf1?/czf1? 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 efg1?/efg1? and czf1?/czf1? 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. |
Databáze: | Supplemental Index |
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