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Antimicrobial Agents and Chemotherapy, April 2006, p. 1148-1155, Vol. 50, No. 4
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.4.1148-1155.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Overexpression of Candida albicans CDR1, CDR2, or MDR1 Does Not Produce Significant Changes in Echinocandin Susceptibility{dagger}

K. Niimi,1 K. Maki,2 F. Ikeda,2 A. R. Holmes,1 E. Lamping,1 M. Niimi,3 B. C. Monk,1 and R. D. Cannon1*

Department of Oral Sciences, University of Otago, Dunedin, New Zealand,1 Astellas Pharma Inc., Osaka,2 Department of Bioactive Molecules, National Institute of Infectious Diseases, Tokyo, Japan3

Received 16 September 2005/ Returned for modification 31 October 2005/ Accepted 23 December 2005

The micafungin and caspofungin susceptibilities of Candida albicans laboratory and clinical isolates and of Saccharomyces cerevisiae strains stably hyperexpressing fungal ATP-binding cassette (ABC) or major facilitator superfamily (MFS) transporters involved in azole resistance were determined using three separate methods. Yeast strains hyperexpressing individual alleles of ABC transporters or an MFS transporter from C. albicans gave the expected resistance profiles for the azoles fluconazole, itraconazole, and voriconazole. The strains hyperexpressing CDR2 showed slightly decreased susceptibility to caspofungin in agar plate drug resistance assays, as previously reported, but increased susceptibility to micafungin compared with either the strains hyperexpressing CDR1 or the null parent deleted of seven ABC transporters. The strains hyperexpressing CDR1 showed slightly decreased susceptibility to micafungin in these assays. A C. albicans clinical isolate overexpressing both Cdr1p and Cdr2p relative to its azole-sensitive isogenic progenitor acquired resistance to azole drugs and showed reduced susceptibility to caspofungin and slightly increased susceptibility to micafungin in agar plate drug resistance assays. None of the strains showed significant resistance to micafungin or caspofungin in liquid microdilution susceptibility assays. The antifungal activities of micafungin and caspofungin were similar in agarose diffusion assays, although the shape and size of the caspofungin inhibitory zones were affected by medium composition. The assessment of micafungin and caspofungin potency is therefore assay dependent; the differences seen with agar plate drug resistance assays occur over narrow ranges of echinocandin concentrations and are not of clinical significance.

* Corresponding author. Mailing address: Molecular Microbiology Laboratory, Department of Oral Sciences, School of Dentistry, University of Otago, P.O. Box 647, 310 Great King Street, Dunedin, New Zealand. Phone: 64 3 479 7081. Fax: 64 3 479 7078. E-mail: richard.cannon{at}stonebow.otago.ac.nz.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.

Antimicrobial Agents and Chemotherapy, April 2006, p. 1148-1155, Vol. 50, No. 4
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.4.1148-1155.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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