The effect of the echinocandin analogue caspofungin on cell wall glucan synthesis by Cryptococcus neoformans

Marta Feldmesser, Yvonne Kress, Aron Mednick, Arturo Casadevall

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

The echinocandin derivative caspofungin (MK-0991, L-743,872) inhibits 1,3-β-D-glucan synthesis and is active against several medically important fungi but is relatively ineffective against Cryptococcus neoformans. To investigate the mechanism of C. neoformans resistance, the prevalence of 1,3- and 1,6-β-D-glucan linkages was determined in cells grown with and without caspofungin, using affinity-purified antisera and gold particle immunoelectron microscopy. Cryptococcal strains ATCC 24067 (serotype D) and MY2061 (serotype A) were studied. Growth at 4 μg/mL of caspofungin reduced both glucan linkages in both strains. However, growth at 2 μg/mL resulted in reduced 1,6-β-D-glucan linkage only for MY2061. Inhibition of 1,6-β-D-glucan synthesis may be an additional mechanism of action for pneumocandins. The relatively low efficacy of caspofungin against C. neoformans may result from reduced activity against C. neoformans glucan synthase or from yet undiscovered mechanisms of action operative in other fungal pathogens but not in C. neoformans.

Original languageEnglish (US)
Pages (from-to)1791-1795
Number of pages5
JournalJournal of Infectious Diseases
Volume182
Issue number6
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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