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380. Drosophila melanogaster as a Facile Model for Large-Scale Studies of Virulence Mechanisms and Antifungal Drug Efficacy in Candida auris Candidiasis

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 with C. albicans. Additionally, studies of drug efficacy against C. auris rely on conventional animal models that ar...

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Autores principales: Bandi, Ashwini, Wurster, Sebastian, Raman, Nitya M, Albert, Nathaniel, Raad, Issam I, Beyda, Nicholas, Kontoyiannis, Dimitrios P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6253174/
http://dx.doi.org/10.1093/ofid/ofy210.391
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author Bandi, Ashwini
Wurster, Sebastian
Raman, Nitya M
Albert, Nathaniel
Raad, Issam I
Beyda, Nicholas
Kontoyiannis, Dimitrios P
author_facet Bandi, Ashwini
Wurster, Sebastian
Raman, Nitya M
Albert, Nathaniel
Raad, Issam I
Beyda, Nicholas
Kontoyiannis, Dimitrios P
author_sort Bandi, Ashwini
collection PubMed
description 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 with 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 Toll(I-RXA)/Toll(r632) female flies with a needle dipped in Candida solutions (10(8) 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. albicansclinical 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 (10(7) to 10(10) 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 with untreated C. auris #0386-infected flies. Interestingly, survival rates were improved in POSA-fed infected flies compared with 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. DISCLOSURES: 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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spelling pubmed-62531742018-11-28 380. Drosophila melanogaster as a Facile Model for Large-Scale Studies of Virulence Mechanisms and Antifungal Drug Efficacy in Candida auris Candidiasis Bandi, Ashwini Wurster, Sebastian Raman, Nitya M Albert, Nathaniel Raad, Issam I Beyda, Nicholas Kontoyiannis, Dimitrios P Open Forum Infect Dis Abstracts 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 with 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 Toll(I-RXA)/Toll(r632) female flies with a needle dipped in Candida solutions (10(8) 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. albicansclinical 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 (10(7) to 10(10) 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 with untreated C. auris #0386-infected flies. Interestingly, survival rates were improved in POSA-fed infected flies compared with 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. DISCLOSURES: 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. Oxford University Press 2018-11-26 /pmc/articles/PMC6253174/ http://dx.doi.org/10.1093/ofid/ofy210.391 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Bandi, Ashwini
Wurster, Sebastian
Raman, Nitya M
Albert, Nathaniel
Raad, Issam I
Beyda, Nicholas
Kontoyiannis, Dimitrios P
380. Drosophila melanogaster as a Facile Model for Large-Scale Studies of Virulence Mechanisms and Antifungal Drug Efficacy in Candida auris Candidiasis
title 380. Drosophila melanogaster as a Facile Model for Large-Scale Studies of Virulence Mechanisms and Antifungal Drug Efficacy in Candida auris Candidiasis
title_full 380. Drosophila melanogaster as a Facile Model for Large-Scale Studies of Virulence Mechanisms and Antifungal Drug Efficacy in Candida auris Candidiasis
title_fullStr 380. Drosophila melanogaster as a Facile Model for Large-Scale Studies of Virulence Mechanisms and Antifungal Drug Efficacy in Candida auris Candidiasis
title_full_unstemmed 380. Drosophila melanogaster as a Facile Model for Large-Scale Studies of Virulence Mechanisms and Antifungal Drug Efficacy in Candida auris Candidiasis
title_short 380. Drosophila melanogaster as a Facile Model for Large-Scale Studies of Virulence Mechanisms and Antifungal Drug Efficacy in Candida auris Candidiasis
title_sort 380. drosophila melanogaster as a facile model for large-scale studies of virulence mechanisms and antifungal drug efficacy in candida auris candidiasis
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6253174/
http://dx.doi.org/10.1093/ofid/ofy210.391
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