title: Toll-deficient Drosophila flies as a fast, high-throughput model for the study of antifungal drug efficacy against invasive aspergillosis and Aspergillus virulence.
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.
authors.affiliation: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Michail S
authors.initials: MS
authors.lastname: Lionakis
authors.forename: Russell E
authors.initials: RE
authors.lastname: Lewis
authors.forename: Gregory S
authors.initials: GS
authors.lastname: May
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Wiederhold
authors.forename: Nathaniel D
authors.initials: ND
authors.lastname: Albert
authors.forename: Georg
authors.initials: G
authors.lastname: Halder
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics / Q000382:microbiology*; D029721:Drosophila Proteins / Q000235:genetics*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D017353:Gene Deletion; D011956:Receptors, Cell Surface / Q000235:genetics*; D051193:Toll-Like Receptors
chemical_list: D000935:Antifungal Agents; D029721:Drosophila Proteins; D011956:Receptors, Cell Surface; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors