CHARACTERIZATION OF HUMAN STEROID-HORMONE TRANSPORT MEDIATED BY CDRLP, A MULTIDRUG TRANSPORTER OF CANDIDA-ALBICANS, BELONGING TO THE ATP BINDING CASSETTE SUPER FAMILY
S. Krishnamurthy et al., CHARACTERIZATION OF HUMAN STEROID-HORMONE TRANSPORT MEDIATED BY CDRLP, A MULTIDRUG TRANSPORTER OF CANDIDA-ALBICANS, BELONGING TO THE ATP BINDING CASSETTE SUPER FAMILY, FEMS microbiology letters, 158(1), 1998, pp. 69-74
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.