Of mice, flies--and men? Comparing fungal infection models for large-scale screening efforts

Disease Models & Mechanisms
Sascha BrunkeDominique Ferrandon

Abstract

Studying infectious diseases requires suitable hosts for experimental in vivo infections. Recent years have seen the advent of many alternatives to murine infection models. However, the use of non-mammalian models is still controversial because it is often unclear how well findings from these systems predict virulence potential in humans or other mammals. Here, we compare the commonly used models, fruit fly and mouse (representing invertebrate and mammalian hosts), for their similarities and degree of correlation upon infection with a library of mutants of an important fungal pathogen, the yeast Candida glabrata. Using two indices, for fly survival time and for mouse fungal burden in specific organs, we show a good agreement between the models. We provide a suitable predictive model for estimating the virulence potential of C. glabrata mutants in the mouse from fly survival data. As examples, we found cell wall integrity mutants attenuated in flies, and mutants of a MAP kinase pathway had defective virulence in flies and reduced relative pathogen fitness in mice. In addition, mutants with strongly reduced in vitro growth generally, but not always, had reduced virulence in flies. Overall, we demonstrate that surveying Drosophila...Continue Reading

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Citations

Jan 19, 2016·Frontiers in Physiology·Lisa C Barros de Andrade E SousaEdda Klipp
Dec 5, 2015·Frontiers in Microbiology·Haroldo C de OliveiraMaria J S Mendes-Giannini
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Jun 24, 2017·Frontiers in Microbiology·Franziska GerwienBernhard Hube
Feb 11, 2020·Frontiers in Immunology·Lianne B CohenSteven A Wasserman
May 19, 2019·Scientific Reports·Vicent Llopis-TorregrosaHana Sychrová
May 6, 2019·Microbiology·Frédéric Devaux, Antonin Thiébaut
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Oct 30, 2021·Frontiers in Genome Editing·Deeva UthayakumarRebecca S Shapiro

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Methods Mentioned

BETA
PCR
glycosylation
scraping
PCRs

Software Mentioned

nnet
GeneSpring GX
TermFinder
R
GraphPad Prism

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