Drosophila melanogaster as a facile model for large-scale studies of virulence mechanisms and antifungal drug efficacy in Candida species.
Candida species are the predominant fungal pathogens in humans and an important cause of mortality in immunocompromised patients. We developed a model of candidiasis in Toll (Tl)-deficient Drosophila melanogaster. Similar to the situation in humans, C. parapsilosis was less virulent than C. albicans when injected into Tl mutant flies. In agreement with findings in the mouse model of invasive candidiasis, cph1/cph1 and efg1/efg1 C. albicans mutants had attenuated virulence, and the efg1/efg1 cph1/cph1 double mutant was almost avirulent in Tl mutant flies. Furthermore, the conditional tet-NRG1 C. albicans strain displayed significantly attenuated virulence in flies fed food without doxycycline; virulence was restored to wild-type levels when the strain was injected into Tl mutant flies fed doxycycline-containing food. Fluconazole (FLC) mixed into food significantly protected Tl mutant flies injected with FLC-susceptible C. albicans strains, but FLC had no activity in flies injected with FLC-resistant C. krusei strains. The D. melanogaster model is a promising minihost model for large-scale studies of virulence mechanisms and antifungal drug activity in candidiasis.
Chamilos
Georgios
G
Department of Infectious Diseases, Infection Control, and Employee Health, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Lionakis
Michail S
MS
Lewis
Russell E
RE
Lopez-Ribot
Jose L
JL
Saville
Stephen P
SP
Albert
Nathaniel D
ND
Halder
Georg
G
Kontoyiannis
Dimitrios P
DP
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology*; D015169:Colony Count, Microbial; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics / Q000382:microbiology*; D025141:Drug Resistance, Fungal; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D051193:Toll-Like Receptors / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics
D000935:Antifungal Agents; C090837:CPH1 protein, Candida albicans; D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; D012097:Repressor Proteins; D051193:Toll-Like Receptors; D014157:Transcription Factors; D037521:Virulence Factors; D015725:Fluconazole