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Antimicrobial Agents and Chemotherapy, November 2008, p. 4057-4063, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.01648-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Enhanced Susceptibility to Antifungal Oligopeptides in Yeast Strains Overexpressing ABC Multidrug Efflux Pumps{triangledown}

Roland Wakiec,1 Iwona Gabriel,1 Rajendra Prasad,2 Jeffrey M. Becker,3 John W. Payne,4 and Slawomir Milewski1*

Department of Pharmaceutical Technology and Biochemistry, Gdansk University of Technology, 11/12 Narutowicza Street, 80-952 Gdansk, Poland,1 Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India,2 Department of Microbiology, University of Tennessee, Knoxville, Tennessee,3 School of Biological Sciences, University of Wales, Bangor, Wales, United Kingdom4

Received 21 December 2007/ Returned for modification 9 February 2008/ Accepted 7 September 2008

The susceptibility to several oligopeptide and amino acid antifungals of a Saccharomyces cerevisiae strain carrying multiple deletions in yeast multidrug resistance genes was compared to transformants containing the CDR1, CDR2, or MDR1 genes that encode the major Candida albicans drug efflux pumps. Recombinant yeast strains overexpressing Cdr1p and Cdr2p showed enhanced susceptibilities to all tested oligopeptide antifungals. The enhanced susceptibilities of multidrug-resistant yeast strains to oligopeptide antifungals corresponded to higher rates of oligopeptide uptake. Yeast cells overexpressing Cdr1p or Cdr2p effluxed protons at higher rates than the reference cells lacking these ABC transporters. An increased plasma membrane electrochemical gradient caused by the functional overexpression of Cdr1p or Cdr2p appeared to increase cellular susceptibility to oligopeptide antifungals by stimulating their uptake via oligopeptide permeases.

* Corresponding author. Mailing address: Department of Pharmaceutical Technology & Biochemistry, Gdansk University of Technology, 11/12 Narutowicza St., 80-952 Gdansk, Poland. Phone: 48 583472107. Fax: 48 583471144. E-mail: milewski{at}altis.chem.pg.gda.pl

{triangledown} Published ahead of print on 15 September 2008.

Antimicrobial Agents and Chemotherapy, November 2008, p. 4057-4063, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.01648-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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