380. Drosophila melanogaster as a Facile Model for Large-Scale Studies of Virulence Mechanisms and Antifungal Drug Efficacy in Candida auris Candidiasis
Session: Poster Abstract Session: Fungal Disease: Management and Outcomes
Thursday, October 4, 2018
Room: S Poster Hall
Background: Candida auris is an emerging multi-drug resistant human pathogen. Experimental data on the pathogenicity of C. auris is scarce, especially regarding its virulence compared to C. albicans. Additionally, studies of drug efficacy against C. auris rely on conventional animal models that are laborious and low throughput; alternative, less cumbersome models are desirable. To that end, we developed a C. auris fly infection model.

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.

Ashwini Bandi, ---1, Sebastian Wurster, MD2, Nitya M Raman, PhD2, Nathaniel Albert, MS2, Issam I Raad, MD, FACP, FIDSA, FSHEA2, Nicholas Beyda, PharmD, BCPS3 and Dimitrios P. Kontoyiannis, MD, ScD, PhD (Hon), FACP, FIDSA, FECMM, FAAM2, (1)St. John's School, Houston, TX, (2)Department of Infectious Diseases Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, (3)University of Houston College of Pharmacy, Houston, TX

Disclosures:

A. Bandi, None

S. Wurster, None

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 .

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