CHARACTERIZATION OF HUMAN STEROID-HORMONE TRANSPORT MEDIATED BY CDRLP, A MULTIDRUG TRANSPORTER OF CANDIDA-ALBICANS, BELONGING TO THE ATP BINDING CASSETTE SUPER FAMILY

Cdr1p, a multidrug transporter from a pathogenic yeast Candida albican s, confers resistance to several unrelated drugs including anti-Candid a drugs. We demonstrate that Cdr1p can specifically transport human st eroid hormones namely beta-estradiol and corticosterone. Saccharomyces cerevisiae transformant S-12, harbouring the CDR1 gene, accumulated a bout 3-fold less [H-3]beta-estradiol and about 2-fold less [H-3]cortic osterone than the non-transformed strain. When CDR1 was expressed in A D strain (AD-CDR1) which had seven ATP binding cassette (ABC) superfam ily of putative transporter genes disrupted, the net accumulation of t hese hormones as compared to S-12 was significantly lower. Efflux of P -estradiol and corticosterone was inhibited by a 100-fold higher (200 nM) concentration of beta-estradiol, corticosterone, ergosterol or dex amethasone, but progesterone which could not be transported by Cdr1p d id not affect the efflux and thus accumulation. Interestingly, some of the drugs viz. cycloheximide, chloramphenicol, fluconazole and o-phen anthroline, to which CDR1 confers resistance, could also prevent efflu x and enhance accumulation to some extent. In conclusion, we show that human steroid hormones could be the substrates for Cdr1p and the ener gy dependent transport mediated by it is specific for estradiol and co rticosterone. (C) 1998 Published by Elsevier Science B.V. All rights r eserved.