Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering
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Type
ArticleKAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Computational Bioscience Research Center (CBRC)
Integrative Systems Biology Lab
Red Sea Research Center (RSRC)
Date
2010-08-24Online Publication Date
2010-08-24Print Publication Date
2010Permanent link to this record
http://hdl.handle.net/10754/334580
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Background: 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.Citation
Kuo 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.Publisher
Springer NatureJournal
Genome BiologyPubMed ID
20653936PubMed Central ID
PMC2926788ae974a485f413a2113503eed53cd6c53
10.1186/gb-2010-11-7-r77
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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/2.0/
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