TY - JOUR
T1 - The effect of the echinocandin analogue caspofungin on cell wall glucan synthesis by Cryptococcus neoformans
AU - Feldmesser, Marta
AU - Kress, Yvonne
AU - Mednick, Aron
AU - Casadevall, Arturo
N1 - Funding Information:
Financial support: National Institutes of Health (grants AI-01341 to M.F.; AI-22774, AI-13342, and HL-59842 to A.C.), Merck (study expense reimbursement to Y.K.); Burroughs Wellcome Fund Scholar Award (to A.C.).
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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U2 - 10.1086/317614
DO - 10.1086/317614
M3 - Article
C2 - 11069257
AN - SCOPUS:0033680483
SN - 0022-1899
VL - 182
SP - 1791
EP - 1795
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -