Attenuation of the activity of caspofungin at high concentrations against candida albicans: possible role of cell wall integrity and calcineurin pathways.
Caspofungin had diminished activity in vitro against Candida albicans at concentrations of 8 to 32 microg/ml. This phenomenon was markedly attenuated in a deltamkc1/deltamkc1 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.
Wiederhold
Nathan P
NP
The University of Texas at Austin College of Pharmacy, 7703 Floyd Curl Dr., MSC 6220, San Antonio, Texas 78229, USA. wiederholdn@uthscsa.edu
Kontoyiannis
Dimitrios P
DP
Prince
Randall A
RA
Lewis
Russell E
RE
D000935:Antifungal Agents / Q000494:pharmacology*; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology; D000077336:Caspofungin; D002473:Cell Wall / Q000187:drug effects* / Q000502:physiology; D004352:Drug Resistance, Microbial / Q000502:physiology*; D054714:Echinocandins; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000494:pharmacology*
D000935:Antifungal Agents; D065095:Calcineurin Inhibitors; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D019703:Calcineurin; D000077336:Caspofungin