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The Candida albicans Cdr2p ATP-binding cassette (ABC) transporter confers resistance to caspofungin

Manuela Schuetzer-Muehlbauer1, Birgit Willinger, Gerd Krapf

  • 1Institute of Medical Biochemistry, Department of Molecular Genetics, University and BioCenter of Vienna, Dr Bohr-Gasse 9/2, A-1030 Vienna, Austria.

Molecular Microbiology
|March 27, 2003
PubMed

Insights

Candida albicans Cdr2p, an ABC transporter, contributes to caspofungin resistance by increasing drug efflux. This finding is crucial for understanding and combating antifungal drug resistance in clinical settings.

Area of Science:

  • Medical Mycology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Multidrug resistance is a significant challenge in antifungal therapy.
  • Candida albicans possesses ATP-binding cassette (ABC) transporters, including Cdr2p, that mediate antifungal resistance via drug efflux.
  • Echinocandins, like caspofungin, are a new class of antifungals targeting fungal cell wall synthesis.

Purpose of the Study:

  • To investigate the role of Candida albicans Cdr2p in caspofungin resistance.
  • To determine if Cdr2p contributes to cross-resistance phenotypes observed in clinical isolates.
  • To elucidate the mechanisms underlying antifungal drug resistance.

Main Methods:

  • Agar plate resistance assays to determine minimal inhibitory concentrations (MICs).
  • Northern analysis and immunoblotting to assess CDR1 and CDR2 gene expression levels.
  • Functional expression of Cdr1p and Cdr2p in Saccharomyces cerevisiae recipient strains.
  • Constitutive overexpression of Cdr2p in a drug-sensitive C. albicans strain.

Main Results:

  • Clinical isolates of C. albicans with cross-resistance showed high MICs to caspofungin.
  • These isolates exhibited elevated CDR1 and CDR2 expression.
  • Expression of Cdr2p, and to a lesser extent Cdr1p, in yeast conferred cross-resistance to azoles and terbinafine.
  • Cdr2p expression led to hyper-resistance to caspofungin in yeast and in C. albicans.
  • Constitutive overexpression of Cdr2p in C. albicans also conferred caspofungin resistance.

Conclusions:

  • Cdr2p, an ABC transporter in Candida albicans, plays a significant role in conferring resistance to caspofungin.
  • Cdr2p may contribute to clinical echinocandin resistance.
  • The observed cross-resistance phenotypes in clinical isolates likely result from multiple, potentially simultaneous, resistance mechanisms.

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