A STE6P P-GLYCOPROTEIN HOMOLOG FROM THE ASEXUAL YEAST CANDIDA-ALBICANS TRANSPORTS THE A-FACTOR MATING PHEROMONE IN SACCHAROMYCES-CEREVISIAE/

In Saccharomyces cerevisiae MATa cells, export of the a-factor mating pheromone is mediated by Ste6p, a member of the ATP-binding cassette ( ABC) superfamily of transporters and a close homologue of mammalian mu ltidrug transporter P-glycoproteins (Pgps), We have used functional co mplementation of a ste6 Delta mutation to isolate a gene encoding an A BC transporter capable of a-factor export from the pathogenic yeast, C andida albicans, This gene codes for a 1323-amino acid protein with an intramolecular duplicated structure, each repeated half containing si x potential hydrophobic transmembrane segments and a hydrophilic domai n with consensus sequences for an ATP-binding fold, The predicted prot ein displays significant sequence similarity to S. cerevisiae Ste6p an d mammalian Pgps, The gene has been named HST6, for homologue of STE6, A high degree of structural conservation between the STE6 and the HST 6 loci with respect to DNA sequence, physical linkage and transcriptio nal arrangement indicates that HST6 is the C. albicans orthologue of t he S. cerevisiae STE6 gene, We show that the HST6 gene is transcribed in a haploid-specific manner in S. cerevisiae, consistent with the pre sence in its promoter of a consensus sequence for Mata1p-Mat alpha 2p binding known to mediate the repression of haploid-specific genes in S . cerevisiae diploid cells, In C. albicans, HST6 is expressed constitu tively at high levels in the different cell types analysed (yeast, hyp hae, white and opaque), demonstrating that HST6 transcription is not r epressed in this diploid yeast, unlike in diploid S. cerevisiae, and s uggesting a basic biological function for the Hst6p transporter in C. albicans. The strong similarity between Hst6p and the multidrug transp orter Pgps also raises the possibility that Hst6p could be involved in resistance to antifungal drugs in C. albicans.