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The Candida albicans Cdr2p ATP‐binding cassette (ABC) transporter confers resistance to caspofungin
Author(s) -
SchuetzerMuehlbauer Manuela,
Willinger Birgit,
Krapf Gerd,
Enzinger Sabine,
Presterl Elisabeth,
Kuchler Karl
Publication year - 2003
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2003.03430.x
Subject(s) - caspofungin , biology , microbiology and biotechnology , candida albicans , echinocandins , atp binding cassette transporter , echinocandin , efflux , yeast , multiple drug resistance , drug resistance , corpus albicans , antifungal drug , antifungal , transporter , biochemistry , gene , amphotericin b , fluconazole
Summary Multidrug resistance may pose a serious problem to antifungal therapy. The Candida albicans Cdr2p is one of two A TP‐ b inding c assette (ABC) transporters mediating antifungal resistance in vivo through increased drug efflux. Echinocandins such as caspofungin represent the newest class of antifungals that target cell wall synthesis. We show here by agar plate resistance assays that cross‐resistant clinical isolates of C. albicans display high minimal inhibitory concentrations (MICs) to caspofungin when compared with a sensitive ATCC reference strain. Northern analysis and immunoblotting indicate that these isolates also show high levels of CDR1 and CDR2 expression. To determine a possible contribution of Cdr1p or Cdr2p to caspofungin resistance, we have functionally expressed Cdr1p and Cdr2p in appropriate recipient strains of the yeast Saccharomyces cerevisiae . Yeast cells expressing Cdr1p or Cdr2p exhibit cross‐resistance to established antifungal drugs such as azoles and terbinafine. However, Cdr2p and, to a much lesser extent, Cdr1p confer caspofungin hyper‐resistance when expressed in yeast. Likewise, Cdr2p confers caspofungin resistance when constitutively overexpressed in a drug‐sensitive C. albicans strain. We therefore propose that Cdr2p may contribute to clinical candin resistance. Finally, our data suggest that cross‐resistance phenotypes of clinical isolates are the consequence of distinct mechanisms that may operate simultaneously.