Fig 1. Linkage between ergosterol biosynthesis and ABC transporter expression.

(A) Aspergillus fumigatus pathway. Ergosterol levels are depleted by azole inhibition of the Cyp51A target enzyme. This in turn leads to proteolytic activation of the SrbA transcription factor, which can then move to its target sites in the nucleus (SRE), leading to the induction of the cyp51A gene. We currently do not know if the AtrR transcription factor is regulated by ergosterol but this factor has been shown to induce transcription of cyp51A, the ABC transporter-encoding gene abcG1, the srbA gene and atrR itself. (B) Candida glabrata pathway. Depletion of ergosterol leads to an accumulation in nuclear-localized Upc2A, which, in turn, binds to the promoters of the ERG11, CDR1, and PDR1 genes. Increased PDR1 transcription leads to a rise in Pdr1 transcription factor levels. This triggers a further autoregulatory induction of PDR1 expression as well as enhanced transcription of CDR1 expression. ABC, ATP-binding cassette; SRE, sterol response elements.