Escape of Candida from caspofungin inhibition at concentrations above the MIC (paradoxical effect) accomplished by increased cell wall chitin; evidence for beta-1,6-glucan synthesis inhibition by caspofungin.
Concentrations above the MIC of caspofungin allow growth of some Candida isolates. A strain demonstrating paradoxical growth was grown in the presence and absence of caspofungin, and the cell wall content was analyzed. Beta-1,3-glucan declined 81% in the presence of caspofungin, as expected. Beta-1,6-glucan declined 73%. Chitin increased 898%, demonstrating a mechanism for paradoxical growth-a rapid shift in the key polymer.
Stevens
David A
DA
Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128-2699, USA. stevens@stanford.edu
Ichinomiya
Masayuki
M
Koshi
Yukako
Y
Horiuchi
Hiroyuki
H
D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification / Q000378:metabolism*; D000077336:Caspofungin; D002473:Cell Wall / Q000378:metabolism; D002686:Chitin / Q000378:metabolism*; D054714:Echinocandins; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000494:pharmacology*; D047071:beta-Glucans / Q000378:metabolism*
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D047071:beta-Glucans; D002686:Chitin; C064197:beta-1,6-glucan; D000077336:Caspofungin