ISSN:
1574-6968
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Biology
Notes:
Abstract (1,3)-β-d-Glucan synthase is a cell wall synthesis enzyme that is the target of cilofungin, an antifungal agent of the lipopeptide class. Cilofungin's glucan synthase inhibitory activity, MIC, and effective dose 50% in a systemic infection mouse model tend to correlate for Candida albicans. This correlation is not seen in Aspergillus fumigatus. MICs for cilofungin against A. fumigatus were consistently 〉 125 μg/ml while the effective dose 50% in a systemic aspergillosis model was determined to be 20.6 mg/kg. To begin to understand this discrepancy, we examined the A. fumigatus glucan synthase. This cell wall enzyme was prepared and its activity was measured by [14C]-glucose incorporation from UDP-[U-14C]glucose into an acid insoluble polymer formed in the presence of α-amylase. Enzyme activity in crude membrane preparations was measured in the presence of several antifungal agents. Enzyme inhibition results showed that 1 μg/ml of papulacandin B, echinochandin B, aculeacin A and cilofungin all inhibited A. fumigatus glucan synthase activity (40–71%) while 1 μg/ml of amphotericin B, fluconazole, ketoconazole and nikkomycin did not affect enzyme activity. A correlation was therefore established between the inhibitory effect of cilofungin on the A. fumigatus glucan synthase and the effective dose 50% obtained in a systemic aspergillosis mouse model.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1574-6968.1993.tb06088.x
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