This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Green, L. J.
Right arrow Articles by Current, W. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Green, L. J.
Right arrow Articles by Current, W. L.

 Previous Article  |  Next Article 

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.


This article has been cited by other articles:

  • Johnson, E. M. (2008). Issues in antifungal susceptibility testing. J Antimicrob Chemother 61: i13-i18 [Abstract] [Full Text]  
  • Sussman, A., Huss, K., Chio, L.-C., Heidler, S., Shaw, M., Ma, D., Zhu, G., Campbell, R. M., Park, T.-S., Kulanthaivel, P., Scott, J. E., Carpenter, J. W., Strege, M. A., Belvo, M. D., Swartling, J. R., Fischl, A., Yeh, W.-K., Shih, C., Ye, X. S. (2004). Discovery of Cercosporamide, a Known Antifungal Natural Product, as a Selective Pkc1 Kinase Inhibitor through High-Throughput Screening. Eukaryot Cell 3: 932-943 [Abstract] [Full Text]  
  • Polonelli, L., Magliani, W., Conti, S., Bracci, L., Lozzi, L., Neri, P., Adriani, D., De Bernardis, F., Cassone, A. (2003). Therapeutic Activity of an Engineered Synthetic Killer Antiidiotypic Antibody Fragment against Experimental Mucosal and Systemic Candidiasis. Infect. Immun. 71: 6205-6212 [Abstract] [Full Text]  
  • Yaakov, G., Bell, M., Hohmann, S., Engelberg, D. (2003). Combination of Two Activating Mutations in One HOG1 Gene Forms Hyperactive Enzymes That Induce Growth Arrest. Mol. Cell. Biol. 23: 4826-4840 [Abstract] [Full Text]  
  • Groll, A. H., Mickiene, D., Petraitis, V., Petraitiene, R., Ibrahim, K. H., Piscitelli, S. C., Bekersky, I., Walsh, T. J. (2001). Compartmental Pharmacokinetics and Tissue Distribution of the Antifungal Echinocandin Lipopeptide Micafungin (FK463) in Rabbits. Antimicrob. Agents Chemother. 45: 3322-3327 [Abstract] [Full Text]  
  • Rex, J. H., Pfaller, M. A., Walsh, T. J., Chaturvedi, V., Espinel-Ingroff, A., Ghannoum, M. A., Gosey, L. L., Odds, F. C., Rinaldi, M. G., Sheehan, D. J., Warnock, D. W. (2001). Antifungal Susceptibility Testing: Practical Aspects and Current Challenges. Clin. Microbiol. Rev. 14: 643-658 [Abstract] [Full Text]  
  • Groll, A. H., Mickiene, D., Petraitiene, R., Petraitis, V., Lyman, C. A., Bacher, J. S., Piscitelli, S. C., Walsh, T. J. (2001). Pharmacokinetic and Pharmacodynamic Modeling of Anidulafungin (LY303366): Reappraisal of Its Efficacy in Neutropenic Animal Models of Opportunistic Mycoses Using Optimal Plasma Sampling. Antimicrob. Agents Chemother. 45: 2845-2855 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»