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

Antimicrob Agents Chemother. 2006 Sep;50(9):3160-1. doi: 10.1128/AAC.00563-06.

Abstract

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.

MeSH terms

  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects*
  • Candida albicans / growth & development
  • Candida albicans / isolation & purification
  • Candida albicans / metabolism*
  • Caspofungin
  • Cell Wall / metabolism
  • Chitin / metabolism*
  • Echinocandins
  • Lipopeptides
  • Microbial Sensitivity Tests
  • Peptides, Cyclic / pharmacology*
  • beta-Glucans / metabolism*

Substances

  • Antifungal Agents
  • Echinocandins
  • Lipopeptides
  • Peptides, Cyclic
  • beta-Glucans
  • Chitin
  • beta-1,6-glucan
  • Caspofungin