TY - JOUR
T1 - Toll-deficient Drosophila flies as a fast, high-throughput model for the study of antifungal drug efficacy against invasive aspergillosis and Aspergillus virulence
AU - Lionakis, Michail S.
AU - Lewis, Russell E.
AU - May, Gregory S.
AU - Wiederhold, Nathan P.
AU - Albert, Nathaniel D.
AU - Halder, Georg
AU - Kontoyiannis, Dimitrios P.
N1 - Funding Information:
Financial support: University of Texas M. D. Anderson Cancer Center (institutional research grant and M. D. Anderson Faculty E. N. Cobb Scholar Award Research Endowment, both to D.P.K.).
PY - 2005/4/1
Y1 - 2005/4/1
N2 - 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.
AB - 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.
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U2 - 10.1086/428587
DO - 10.1086/428587
M3 - Article
C2 - 15747256
AN - SCOPUS:15544363784
SN - 0022-1899
VL - 191
SP - 1188
EP - 1195
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 7
ER -