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Antimicrobial Agents and Chemotherapy, February 2008, p. 694-704, Vol. 52, No. 2
0066-4804/08/$08.00+0     doi:10.1128/AAC.00861-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Multidrug Transporters CaCdr1p and CaMdr1p of Candida albicans Display Different Lipid Specificities: both Ergosterol and Sphingolipids Are Essential for Targeting of CaCdr1p to Membrane Rafts{triangledown}

Ritu Pasrija,1,{dagger} Sneh Lata Panwar,2 and Rajendra Prasad1*

Membrane Biology,1 Yeast Genetics Laboratories, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India2

Received 2 July 2007/ Returned for modification 10 September 2007/ Accepted 16 November 2007

In this study, we compared the effects of altered membrane lipid composition on the localization of two membrane drug transporters from different superfamilies of the pathogenic yeast Candida albicans. We demonstrated that in comparison to the major facilitator superfamily multidrug transporter CaMdr1p, ATP-binding cassette transporter CaCdr1p of C. albicans is preferentially localized within detergent-resistant membrane (DRM) microdomains called ‘rafts.’ Both CaCdr1p and CaMdr1p were overexpressed as green fluorescent protein (GFP)-tagged proteins in a heterologous host Saccharomyces cerevisiae, wherein either sphingolipid ({Delta}sur4 or {Delta}fen1 or {Delta}ipt1) or ergosterol ({Delta}erg24 or {Delta}erg6 or {Delta}erg4) biosynthesis was compromised. CaCdr1p-GFP, when expressed in the above mutant backgrounds, was not correctly targeted to plasma membranes (PM), which also resulted in severely impaired drug resistance. In contrast, CaMdr1p-GFP displayed no sorting defect in the mutant background and remained properly surface localized and displayed no change in drug resistance. Our data clearly show that CaCdr1p is selectively recruited, over CaMdr1p, to the DRM microdomains of the yeast PM and that any imbalance in the raft lipid constituents results in missorting of CaCdr1p.

* Corresponding author. Mailing address: Jawaharlal Nehru University, School of Life Sciences, JNU Campus, New Mehrauli Road, New Delhi 110067, India. Phone: 91-11-2670-4509. Fax: 91-11-2674-1081. E-mail: rp47{at}mail.jnu.ac.in

{triangledown} Published ahead of print on 3 December 2007.

{dagger} Present address: Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar, India.

Antimicrobial Agents and Chemotherapy, February 2008, p. 694-704, Vol. 52, No. 2
0066-4804/08/$08.00+0     doi:10.1128/AAC.00861-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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