Schematic diagrams of ergosterol biosynthesis pathways in the absence and in the presence of subinhibitory concentrations of fluconazole.

Sterol intermediates in bold signify their accumulation, the Erg proteins highlighted in blue signify the downregulation of the encoding ERG gene in the Δtlo mutant relative to the WT strain. In the absence of the drug, several toxic intermediates of the ergosterol biosynthesis pathway accumulated in the Δtlo mutant, such as lanosterol, 4,4-dimethyl cholesta-8, 14, 24-trienol, zymosterol, fecosterol and episterol. The accumulation of these intermediates coincides with the down regulation of the ERG genes encoding enzymes that catalyses their conversion, which are highlighted in blue (A). In the presence of the fluconazole, the build-up of these toxic sterol intermediates in the Δtlo mutant is alleviated, although differential ERG6 expression contributes to the build-up of lanosterol in the Δtlo mutant (B).

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