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Antimicrobial Agents and Chemotherapy, December 2005, p. 5146-5148, Vol. 49, No. 12
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.12.5146-5148.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Attenuation of the Activity of Caspofungin at High Concentrations against Candida albicans: Possible Role of Cell Wall Integrity and Calcineurin Pathways

Nathan P. Wiederhold,3,4* Dimitrios P. Kontoyiannis,1,2 Randall A. Prince,1,2 and Russell E. Lewis1

The University of Houston College of Pharmacy,1 The University of Texas M. D. Anderson Cancer Center, Houston, Texas,2 The University of Texas at Austin College of Pharmacy, Austin, Texas,3 The University of Texas Health Science Center at San Antonio, San Antonio, Texas4

Received 25 July 2005/ Returned for modification 6 September 2005/ Accepted 10 September 2005

Caspofungin had diminished activity in vitro against Candida albicans at concentrations of 8 to 32 µg/ml. This phenomenon was markedly attenuated in a {Delta}mkc1/{Delta}mkc1 deletion mutant and by the addition of cyclosporine to the wild type. Short exposure to these caspofungin concentrations resulted in MKC1 up-regulation, suggesting roles of cell wall integrity and calcineurin pathways.

* Corresponding author. Mailing address for Nathan P. Wiederhold: University of Texas at Austin College of Pharmacy, 7703 Floyd Curl Dr., MSC 6220, San Antonio, TX 78229. Phone: (210) 567-8340. Fax: (210) 567-8328. E-mail: wiederholdn{at}uthscsa.edu. Mailing address for Russell E. Lewis: University of Houston College of Pharmacy, 1441 Moursund Street, no. 423, Houston, TX 77030. Phone: (713) 795-8326. Fax: (713) 795-8383. E-mail: rlewis{at}uh.edu.

Antimicrobial Agents and Chemotherapy, December 2005, p. 5146-5148, Vol. 49, No. 12
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.12.5146-5148.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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