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Antimicrobial Agents and Chemotherapy, April 1999, p. 830-835, Vol. 43, No. 4
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

LY303366 Exhibits Rapid and Potent Fungicidal Activity in Flow Cytometric Assays of Yeast Viability

Lisa J. Green,* Philip Marder, Larry L. Mann, Li-Chun Chio, and William L. Current

Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285

Received 21 October 1998/Returned for modification 14 December 1998/Accepted 12 January 1999

LY303366 is a semisynthetic analog of the antifungal lipopeptide echinocandin B that inhibits (1,3)-beta -D-glucan synthase and exhibits efficacy in animal models of human fungal infections. In this study, we utilized flow cytometric analysis of propidium iodide uptake, single-cell sorting, and standard microbiological plating methods to study the antifungal effect of LY303366 on Saccharomyces cerevisiae and Candida albicans. Our data indicate that an initial 5-min pulse treatment with LY303366 caused yeasts to take up propidium iodide and lose their ability to grow. Amphotericin B and cilofungin required longer exposure periods (30 and 180 min, respectively) and higher concentrations to elicit these fungicidal effects. These two measurements of fungicidal activity by LY303366 were highly correlated (r > 0.99) in concentration response and time course experiments. As further validation, LY303366-treated yeasts that stained with propidium iodide were unable to grow in single-cell-sorted cultures. Our data indicate that LY303366 is potent and rapidly fungicidal for actively growing yeasts. The potency and rapid action of this new fungicidal compound suggest that LY303366 may be useful for antifungal therapy.

* Corresponding author. Mailing address: DC0444, Lilly Corporate Center, Indianapolis, IN 46285. Phone: (317) 276-6048. Fax: (317) 277-2934. E-mail: Green_Lisa_J{at}lilly.com.

Antimicrobial Agents and Chemotherapy, April 1999, p. 830-835, Vol. 43, No. 4
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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