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

Citation
M. Feldmesser et al., The effect of the echinocandin analogue caspofungin on cell wall glucan synthesis by Cryptococcus neoformans, J INFEC DIS, 182(6), 2000, pp. 1791-1795
Citations number
15
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Clinical Immunolgy & Infectious Disease",Immunology
Journal title
JOURNAL OF INFECTIOUS DISEASES
ISSN journal
0022-1899 → ACNP
Volume
182
Issue
6
Year of publication
2000
Pages
1791 - 1795
Database
ISI
SICI code
0022-1899(200012)182:6<1791:TEOTEA>2.0.ZU;2-V
Abstract
The echinocandin derivative caspofungin (MK-0991, L-743,872) inhibits 1,3-b eta -D-glucan synthesis and is active against several medically important f ungi but is relatively ineffective against Cryptococcus neoformans, To inve stigate the mechanism of C. neoformans resistance, the prevalence of 1,3- a nd 1,6-beta -D-glucan linkages was determined in cells grown with and witho ut caspofungin, using affinity-purified antisera and gold particle immunoel ectron microscopy. Cryptococcal strains ATCC 24067 (serotype D) and MY2061 (serotype A) were studied. Growth at 4 mug/mL of caspofungin reduced both g lucan linkages in both strains, However, growth at 2 mug/mL resulted in red uced 1,6-beta -D-glucan linkage only for MY2061, Inhibition of 1,6-beta -D- glucan synthesis may be an additional mechanism of action for pneumocandins , The relatively low efficacy of caspofungin against C. neoformans may resu lt from reduced activity against C. neoformans glucan synthase or from yet undiscovered mechanisms of action operative in other fungal pathogens but n ot in C. neoformans.