Efficacy of Voriconazole in Experimental Aspergillosis in Drosophila

M. S. LIONAKIS, G. HALDER, R. E. LEWIS, N. P. WIEDERHOLD, D. P. KONTOYIANNIS

Author address: 

The University of Texas M.D. Anderson Cancer Center, Houston, TX.

Abstract: 

Background: The use of conventional animal models (mice, rats, rabbits) to study the activity of drugs in invasive aspergillosis (IA) is laborious and relies on testing in limited numbers of animals. Alternative, less cumbersome in vivo models are desirable. The Toll innate immunity pathway of Drosophila fruit fly is conserved from non-vertebrates to humans. Tlr632/TlI-RXA mutant flies are highly susceptible to IA compared to wild type flies. Methods: We used three models of infection with A. fumigatus (isolate AF293) in Tlr632/TlI-RXA flies; a) by injection with a needle dipped in a 107 conidia/ml solution (injection assay), b) by rolling on agar plates with conidia for 2 min (rolling assay) and c) by feeding with conidia for 8 hrs (ingestion assay). We assessed the efficacy of voriconazole (VRC) in AF293-infected flies. Flies were pre-exposed to VRC (mixed with fly food) for 1 day, were then infected by either of the three assays, and were fed with VRC-containing food for 8 days post-infection. AF293-infected flies not exposed to VRC were used as controls. Survival was assessed 8 days after infection. Each infection model experiment was done in triplicate using ~50 flies per experiment. In addition to survival, fungal burden was assessed by quantitative PCR (qPCR), histopathology and electron microscopy (EM). A bioassay was performed to confirm VRC exposure in VRC-fed flies. Results: AF293-infected Tlr632/TlI-RXA mutant flies exposed to VRC had significantly better survival (61%, 63% and 50% by injection, rolling and ingestion assay respectively) compared to flies not VRC-exposed (16%, 24% and 12% respectively, P
2004

abstract No: 

M-1139-200

Full conference title: 

44th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 44th