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Antimicrobial Agents and Chemotherapy, October 2003, p. 3305-3310, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3305-3310.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Sensitive Assay for Antifungal Activity of Glucan Synthase Inhibitors That Uses Germ Tube Formation in Candida albicans as an End Point

Timothy G. Brayman* and John W. Wilks{dagger}

Cell and Molecular Biology, Pharmacia Corporation, Kalamazoo, Michigan 49001

Received 9 September 2002/ Returned for modification 28 January 2003/ Accepted 8 July 2003

We implemented a simple, sensitive, objective, and rapid cellular assay to reveal the antifungal activity of a novel class of glucan synthase inhibitors. The assay, especially useful for early drug discovery, measures the transformation of Candida albicans from the yeast form to the hyphal form. Test compounds were ranked by potency (50% inhibitory concentration) and efficacy (percent inhibition of germ tube formation); the intra-assay coefficients of variation for these parameters were 17 and 5%, respectively. The germ tube formation assay proved useful for the early-stage antifungal characterization of a novel class of glucan synthase inhibitors discovered at Pharmacia. Drug concentrations required in this assay to inhibit germ tube formation were lower for 90% of the novel compounds than the concentrations required to determine MICs. The method may have utility for other mechanistic classes of antifungal compounds during the hit-to-lead transition of drug discovery.

* Corresponding author. Mailing address: Cell and Molecular Biology, Pharmacia Corporation, Kalamazoo, MI 49001. Phone: (616) 833-5655. Fax: (616) 833-4255. E-mail: timothy.g.brayman{at}pharmacia.com.

{dagger} Retired.

Antimicrobial Agents and Chemotherapy, October 2003, p. 3305-3310, Vol. 47, No. 10
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.10.3305-3310.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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