Semisynthetic echinocandins affect cell wall deposition of Pneumocystis carinii in vitro and in vivo

Marilyn S. Bartlett, William L. Current, Michael P. Goheen, Carole J. Boylan, Chao H. Lee, Margaret M. Shaw, Sherry F. Queener, James W. Smith

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Cyclic lipodepsipeptide compounds of the echinocandin class exhibit broad-spectrum antifungal activity and have been shown to be effective in the treatment of Pneumocystis carinii pneumonia in laboratory animal models. Previous studies have led investigators to propose that these compounds, active against fungal cell walls, are selectively active against the cyst forms of P. carinii. We demonstrate that a semisynthetic, water-soluble echinocandin analog, LY307853, is effective in reducing the numbers of all life cycle forms of P. carinii and is more effective in mice immunosuppressed with monoclonal antibody to L3T4+ cells than in mice immunosuppressed with dexamethasone. Treatment of P. carinii isolates with LY307853 in a short- term in vitro culture model resulted in cytoarchitectural alterations suggesting that this echinocandin may interfere with the export of surface glycoprotein and the formation of the tubular elements normally found on the surfaces of trophic forms. The cytoarchitectural changes in trophic forms treated in vitro with LY307853 were also observed in trophic forms in the lung tissue of rats treated with a closely related echinocandin analog, LY303366.

Original languageEnglish (US)
Pages (from-to)1811-1816
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume40
Issue number8
DOIs
StatePublished - Aug 1996

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Bartlett, M. S., Current, W. L., Goheen, M. P., Boylan, C. J., Lee, C. H., Shaw, M. M., Queener, S. F., & Smith, J. W. (1996). Semisynthetic echinocandins affect cell wall deposition of Pneumocystis carinii in vitro and in vivo. Antimicrobial Agents and Chemotherapy, 40(8), 1811-1816. https://doi.org/10.1128/aac.40.8.1811