Toll-deficient Drosophila flies as a fast, high-throughput model for the study of antifungal drug efficacy against invasive aspergillosis and Aspergillus virulence

Michail S. Lionakis, Russell E. Lewis, Gregory S. May, Nathan Wiederhold, Nathaniel D. Albert, Georg Halder, Dimitrios P. Kontoyiannis

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Invasive aspergillosis (IA) is the most important opportunistic mycosis in immunosuppressed patients. The lack of a sufficient number of effective antifungals and our incomplete understanding of the pathogenesis of IA contribute to its overall unfavorable prognosis. Studies of drug efficacy against IA and Aspergillus virulence rely on conventional animal models that are laborious and use limited numbers of animals; alternative, less cumbersome in vivo models are desirable. Using different inoculation models of IA, we found that Toll-deficient Drosophila flies exposed to voriconazole (VRC), the preferred drug for the treatment of IA in humans, had significantly better survival rates and lower tissue fungal burdens than did those not exposed to VRC. Furthermore, Toll-deficient Drosophila flies infected with an alb1-deleted hypovirulent Aspergillus mutant had significantly better survival rates than did those infected with a wild-type Aspergillus strain. Therefore, the Drosophila fly is a fast, high-throughput in vivo model for the study of drug efficacy against IA and Aspergillus virulence.

Original languageEnglish (US)
Pages (from-to)1188-1195
Number of pages8
JournalJournal of Infectious Diseases
Volume191
Issue number7
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

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Aspergillosis
Aspergillus
Drosophila
Virulence
Diptera
Pharmaceutical Preparations
Survival Rate
Mycoses
Animal Models

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Toll-deficient Drosophila flies as a fast, high-throughput model for the study of antifungal drug efficacy against invasive aspergillosis and Aspergillus virulence. / Lionakis, Michail S.; Lewis, Russell E.; May, Gregory S.; Wiederhold, Nathan; Albert, Nathaniel D.; Halder, Georg; Kontoyiannis, Dimitrios P.

In: Journal of Infectious Diseases, Vol. 191, No. 7, 01.04.2005, p. 1188-1195.

Research output: Contribution to journalArticle

Lionakis, Michail S. ; Lewis, Russell E. ; May, Gregory S. ; Wiederhold, Nathan ; Albert, Nathaniel D. ; Halder, Georg ; Kontoyiannis, Dimitrios P. / Toll-deficient Drosophila flies as a fast, high-throughput model for the study of antifungal drug efficacy against invasive aspergillosis and Aspergillus virulence. In: Journal of Infectious Diseases. 2005 ; Vol. 191, No. 7. pp. 1188-1195.
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