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Antimicrobial Agents and Chemotherapy, October 2004, p. 3845-3849, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3845-3849.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Caspofungin Uptake Is Mediated by a High-Affinity Transporter in Candida albicans

Padmaja Paderu, Steven Park, and David S. Perlin*

Public Health Research Institute at the International Center for Public Health, Newark, New Jersey

Received 2 April 2004/ Returned for modification 14 May 2004/ Accepted 18 June 2004

The uptake of the echinocandin drug caspofungin acetate in Candida albicans was evaluated at drug levels at or near the MIC for the organism. Maximal uptake was achieved in 10 min and was energy independent. A saturable transport system, consistent with a facilitated-diffusion carrier, was observed with the unlabeled drug competing with the labeled drug for uptake and efflux. More than 90% of the transported drug was observed in a single kinetic compartment that was available for efflux, indicating that the drug was free in the cytoplasm following uptake. Efflux was also energy independent but was sensitive to the presence of a fully loaded carrier on both faces of the bilayer. Overall, the data presented are consistent with the presence of a high-affinity facilitated-diffusion transporter that mediates caspofungin uptake and could be a potential source of transport-related reduced susceptibility.

* Corresponding author. Mailing address: Public Health Research Institute at the International Center for Public Health, 225 Warren St., Newark, NJ 07103. Phone: (973) 854-3200. Fax: (973) 854-3101. E-mail: perlin{at}phri.org.

Antimicrobial Agents and Chemotherapy, October 2004, p. 3845-3849, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3845-3849.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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