Methods: We injected 2 week-old TollI-RXA/Tollr632 female flies with a needle dipped in Candida solutions (108 yeast cells/mL) in the dorsal side of the thorax. Flies were infected with 10 different C. auris strains (source: CDC/FDA) and a C. albicans clinical strain. For drug protection studies, C. auris isolate AR-BANK#0386 [MICs: fluconazole (FLC) > 64, posaconazole (POSA) 0.125-0.25, isavuconazole (ISA) 0.25-1, voriconazole (VRC) 0.5-2 µg/mL)] was used. We assessed survival differences associated with different inocula (107 to 1010 yeast cells/mL) and yeast strains. Moreover, protection conferred by addition of FLC, VRC, ISA, POSA, or FLC combined with 5-FC (flucytosine) and/or nikkomycin Z (NikZ) to fly food was studied. Three independent runs were performed for each experiment.
Results: A) All C. auris strains and C. albicans exhibited comparable in vitro growth rates. B) All strains of C. auris were similarly more virulent than C. albicans (P<0.0001), with all flies dying by day 7 post-infection. C) FLC, VRC, ISA, FLC+5-FC, FLC+NikZ, or FLC+NikZ+5-FC-fed flies infected with C. auris #0386 had comparably poor survival outcomes compared to untreated C. auris #0386-infected flies. Interestingly, survival rates were improved in POSA-fed infected flies compared to FLC-treated or untreated infected flies (P<0.0001). As POSA is a cell-associated drug, we are conducting C. auris phagocytosis assays with Drosophila hemocytes that are co-incubated or not with POSA.
Conclusion: Drosophila is a promising, fast, and inexpensive in-vivo model to study pathogenesis and drug activity in C. auris candidiasis.
N. M. Raman, None
N. Albert, None
I. I. Raad, None
N. Beyda, Astellas: Scientific Advisor , Grant recipient .
D. P. Kontoyiannis, Merck: Consultant , Research support and Speaker honorarium . Pfizer: Consultant , Research support . Astellas: Consultant , Research support and Speaker honorarium . Gilead: Speaker's Bureau , Speaker honorarium . F2G Inc: Speaker's Bureau , Speaker honorarium . Cidara Inc: Speaker's Bureau , Speaker honorarium . Jazz Pharmaceuticals: Speaker's Bureau , Speaker honorarium .