The antifungal antibiotic, ambruticin, inhibits growth of Candida parapsilosis and reduces its ability to take up amino acids. Increasing growth temperature from 30°C to 390C leads to a 100-fold decrease in the minimum growth inhibitory concentration. Ambruticin is 20 times more effective at pH 5 than at pH 8 and exponentially growing cultures are much less susceptible than stationary phase cells. The activity of ambruticin is also dependent on the presence of certain exogenous nutrients. When acetate or succinate (10 mM) are included in the incubation medium, ambruticin has little effect on amino acid uptake. Glucose, mannose and glycerol do not decrease the efficacy of ambruticin. Ambruticin probably inhibits growth by reducing the utilization of exogenous and intracellular carbohydrates. This leads to a fall in energy production within the cell which can be monitored as a reduction in the activity of energy-dependent transport systems.Ambruticin is an antibiotic of novel structure produced by the myxobacterium, Polyangium cellulosum var.fulvum [14]. It is a cyclopropyl-polyene-pyran-acid and its absolute configuration has been determined by X-ray crystallography and partial chiral synthesis [2,9]. Ambruticin possesses very little antibacterial activity but is active in vitro and in vivo against dermatophytes [13,15]. It inhibits the growth of Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis and Candida parapsilosis but has little effect on Paracoccidioides brasiliensis, Cryptococcus neoforroans or C. albicans [11,13].Ambruticin is fungicidal to Microsporum fulvum at 370C but not 4°C and is more active against spores than pregrown hyphae. It does not cause leakage of intracellular material but decreases the incorporation of exogenous uridine and leucine into macromolecules [13]. This paper reports the results of an investigation into the effects of ambruticin on growth and amino acid uptake in C. parapsilosis. This organism was chosen in preference to filamentous dermatophytes because of its ability to grow rapidly and homogeneously in defined liquid media.Correspondence address: 100 Rampton Road, Willingham, Cambridge CB4 5JQ, U.K.
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