Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering
Supplemental File 1
Microsoft Excel 2007
Supplemental File 2
Microsoft Excel 2007
Supplemental File 3
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Computational Bioscience Research Center (CBRC)
Red Sea Research Center (RSRC)
MetadataShow full item record
AbstractBackground: Fungal infections are an emerging health risk, especially those involving yeast that are resistant to antifungal agents. To understand the range of mechanisms by which yeasts can respond to anti-fungals, we compared gene expression patterns across three evolutionarily distant species - Saccharomyces cerevisiae, Candida glabrata and Kluyveromyces lactis - over time following fluconazole exposure. Results: Conserved and diverged expression patterns were identified using a novel soft clustering algorithm that concurrently clusters data from all species while incorporating sequence orthology. The analysis suggests complementary strategies for coping with ergosterol depletion by azoles - Saccharomyces imports exogenous ergosterol, Candida exports fluconazole, while Kluyveromyces does neither, leading to extreme sensitivity. In support of this hypothesis we find that only Saccharomyces becomes more azole resistant in ergosterol-supplemented media; that this depends on sterol importers Aus1 and Pdr11; and that transgenic expression of sterol importers in Kluyveromyces alleviates its drug sensitivity. Conclusions: We have compared the dynamic transcriptional responses of three diverse yeast species to fluconazole treatment using a novel clustering algorithm. This approach revealed significant divergence among regulatory programs associated with fluconazole sensitivity. In future, such approaches might be used to survey a wider range of species, drug concentrations and stimuli to reveal conserved and divergent molecular response pathways.
CitationKuo D, Tan K, Zinman G, Ravasi T, Bar-Joseph Z, et al. (2010) Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering. Genome Biology 11: R77. doi:10.1186/gb-2010-11-7-r77.
PubMed Central IDPMC2926788
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/2.0/
- Cyclic AMP signaling pathway modulates susceptibility of candida species and Saccharomyces cerevisiae to antifungal azoles and other sterol biosynthesis inhibitors.
- Authors: Jain P, Akula I, Edlind T
- Issue date: 2003 Oct
- UPC2A is required for high-level azole antifungal resistance in Candida glabrata.
- Authors: Whaley SG, Caudle KE, Vermitsky JP, Chadwick SG, Toner G, Barker KS, Gygax SE, Rogers PD
- Issue date: 2014 Aug
- Genome-wide expression profiling reveals genes associated with amphotericin B and fluconazole resistance in experimentally induced antifungal resistant isolates of Candida albicans.
- Authors: Barker KS, Crisp S, Wiederhold N, Lewis RE, Bareither B, Eckstein J, Barbuch R, Bard M, Rogers PD
- Issue date: 2004 Aug
- Sterol uptake and sterol biosynthesis act coordinately to mediate antifungal resistance in Candida glabrata under azole and hypoxic stress.
- Authors: Li QQ, Tsai HF, Mandal A, Walker BA, Noble JA, Fukuda Y, Bennett JE
- Issue date: 2018 May