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Comparative genomic hybridization by array of east haploid and heterozygous essential deletion pools treated with compounds synergistic with fluconazole to identify sensitive and resistant mutants

ABSTRACT: The haploid and the heterozygous essential S.cerevisiae deletion pools were grown in the presence of compounds that we found to be synergistic with fluconazole. We also treated the deletion pools with combinations of those drugs and fluconazole to interrogate the mechanism of action of the drug interactions. These experimental samples were hybridized against DMSO or water control samples. The resulting hybridization pattern informs about sensitive and resistant yeast deletion mutants.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Michaela Spitzer

PROVIDER: E-MTAB-394 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Cross-species discovery of syncretic drug combinations that potentiate the antifungal fluconazole.

Spitzer Michaela M Griffiths Emma E Blakely Kim M KM Wildenhain Jan J Ejim Linda L Rossi Laura L De Pascale Gianfranco G Curak Jasna J Brown Eric E Tyers Mike M Wright Gerard D GD

Molecular systems biology 20110621

Resistance to widely used fungistatic drugs, particularly to the ergosterol biosynthesis inhibitor fluconazole, threatens millions of immunocompromised patients susceptible to invasive fungal infections. The dense network structure of synthetic lethal genetic interactions in yeast suggests that combinatorial network inhibition may afford increased drug efficacy and specificity. We carried out systematic screens with a bioactive library enriched for off-patent drugs to identify compounds that pot ...[more]

PMID: 21694716

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