Membrane fluidity affects functions of Cdr1p, a multidrug ABC transporter of Candida albicans.
Earlier, we have shown that the overexpression of an ABC transporter, CDR1, is involved in the emergence of multidrug resistance in Candida albicans. In this study, we checked its function in vivo by expressing it in different isogenic Saccharomyces cerevisiae erg mutants, which accumulated various intermediates of the ergosterol biosynthesis and thus altered the membrane fluidity. Functions like the accumulation of rhodamine 123, beta-estradiol, fluconazole and floppase activity associated with Cdr1p were measured to ascertain their responses to an altered membrane phase. The floppase activity appeared to be favoured by an enhanced membrane fluidity, while the effluxing of substrates and Cdr1p's ability to confer multidrug resistance were significantly reduced. We demonstrate that only some of the functions of Cdr1p were affected by an altered lipid environment.
Smriti
Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Krishnamurthy
S S
SS
Prasad
R
R
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002176:Candida albicans / Q000502:physiology*; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D004875:Ergosterol / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D015725:Fluconazole / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D008560:Membrane Fluidity / Q000502:physiology*; D026901:Membrane Transport Proteins; D012235:Rhodamines / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014170:Transformation, Genetic
D018528:ATP-Binding Cassette Transporters; C094693:CDR1 protein, Candida albicans; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D012235:Rhodamines; D004958:Estradiol; D015725:Fluconazole; D004875:Ergosterol