Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering.

Genome Biology
Dwight KuoTrey Ideker

Abstract

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. 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. We have compared the dynamic transcriptional responses of three diverse yeast species to fluconazole treatment using a novel clustering algorithm...Continue Reading

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Dec 5, 2012·Antimicrobial Agents and Chemotherapy·Luis Vale SilvaDominique Sanglard
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Aug 9, 2011·Comptes rendus biologies·Gaëlle LelandaisFrédéric Devaux
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Jun 13, 2020·Antibiotics·Somanon BhattacharyaBettina C Fries
Mar 20, 2021·Applied Microbiology and Biotechnology·Cindy VallièresSimon V Avery
Apr 15, 2021·FEMS Yeast Research·Catherine TesnièreJean-Luc Legras

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Datasets Mentioned

BETA
GSE15710

Methods Mentioned

BETA
gene knockout
transgenic
PCR

Software Mentioned

VERA
MultiParanoid

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