Glucan synthesis and its inhibition by cilofungin in susceptible and resistant strains of Candida albicans.
The lipopeptide antimycotic agent, cilofungin, at a dose of 20 micrograms ml-1, inhibited beta 1-3 glucan synthesis in a drug-susceptible strain (3153; minimum inhibitory concentration (MIC) < 1 microgram ml-1) as well as in a drug-resistant strain of Candida albicans (CA-2, derived from 3153 by nitrosoguanidine mutagenesis; MIC > 50 micrograms ml-1). This was demonstrated for both whole cells under growing and non-growing conditions, and during protoplast regeneration. However, time-effect experiments, during growth of a CA-2 culture initially exposed to an inhibitory dose of cilofungin, showed that this strain was able to progressively regain both glucan synthesis and a growth rate comparable to that of cultures that had not been treated with the drug. This recovery was not attributable to cilofungin instability or degradation within the CA-2 culture. Our study suggests the existence of an as yet unknown drug-related and/or cell-related factor(s) modulating the inhibition of glucan synthesis, and then contributing to the actual inhibitory effects of cilofungin in C. albicans.
Angiolella
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L
Chair of Microbiology, Faculty of Pharmaceutical Sciences, University of Rome La Sapienza, Italy.
Bromuro
C
C
Simonetti
N
N
Cassone
A
A
D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004352:Drug Resistance, Microbial; D054714:Echinocandins; D005936:Glucans / Q000096:biosynthesis*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011523:Protoplasts / Q000187:drug effects / Q000378:metabolism; D047071:beta-Glucans
D000935:Antifungal Agents; D054714:Echinocandins; D005936:Glucans; D010456:Peptides, Cyclic; D047071:beta-Glucans; C042101:cilofungin; C033363:beta-1,3-glucan