Mutations in <i>HSP90</i> confer resistance to azole and geldanamycin in two <i>S. cerevisiae</i> lineages and in one <i>C. albicans</i> lineage.

<p> (A) Sc-G-12 (right panel) and Sc-G-14 (left panel) are both resistant to azole and geldanamycin and slightly cross-resistant to azole and radicicol, relative to their parental strains (above). (B) Resistance to azole and geldanamycin in Sc-G-14 is attributable to <i>HSC82^I117N</i>. Replacing the ancestral allele with the <i>HSC82^I117N</i> allele expressed on a plasmid increases resistance of the ancestral strain to the level observed in Sc-G-14, while replacing the <i>HSC82^I117N</i> allele with the ancestral allele on a plasmid abrogates resistance of Sc-G-14. (C) Deletion of <i>HSC82</i> in Sc-G-12 or its parental strain phenocopies resistance of Sc-G-12, suggesting that <i>HSC82^K385*</i> confers resistance by loss of function of <i>HSC82</i>. (D) Ca-G-10 has increased resistance to azole and geldanamycin but no cross-resistance to azole and FK506 or azole and radicicol. (E) Resistance to azole and geldanamycin in Ca-G-10 is attributable to <i>HSP90^D91Y</i>. Replacing the native <i>HSP90</i> allele in parental strain with <i>HSP90^D91Y</i> phenocopied resistance of Ca-G-10. Conversely, resistance of Ca-G-10 was abrogated when <i>HSP90^D91Y</i> was replaced with the ancestral <i>HSP90</i> allele. Resistance assays were performed and analyzed is in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003390#pgen-1003390-g002" target="_blank">Figure 2</a>, after incubation at 30°C for 2 days (D) or 3 days (A–C, E). Assays were performed in YPD (A, C–E) or SD with amino acid supplements (B). GdA = geldanamycin; RAD = radicicol; and FL = fluconazole.