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Updated: Apr 16, 2026
Broth Microdilution In Vitro Screening: An Easy and Fast Method to Detect New Antifungal Compounds
Published on: February 14, 2018
Of mice, flies--and men? Comparing fungal infection models for large-scale screening efforts
Sascha Brunke1, Jessica Quintin2, Lydia Kasper3
1Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), University Hospital, 07747 Jena, Germany Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, 07745 Jena, Germany sascha.brunke@leibniz-hki.de.
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 survival after infection is a suitable model to predict the outcome of murine infections, especially for severely attenuated C. glabrata mutants. Pre-screening of mutants in an invertebrate Drosophila model can, thus, provide a good estimate of the probability of finding a strain with reduced microbial burden in the mouse host.
Insights
Fruit fly (Drosophila) infection models effectively predict outcomes in mouse models for studying Candida glabrata virulence. This invertebrate model offers a reliable pre-screening tool for identifying fungal pathogen strains with reduced virulence potential.
Area of Science:
- Microbiology
- Infectious Diseases
- Pathogen Virulence Studies
Background:
- Infectious disease research relies on appropriate in vivo models.
- Non-mammalian models are increasingly used but their predictive value for mammalian virulence is debated.
- Comparing invertebrate (fruit fly) and mammalian (mouse) models for pathogen studies is crucial.
Purpose of the Study:
- To compare the predictive accuracy of fruit fly (Drosophila) and mouse models for Candida glabrata virulence.
- To establish a correlation between C. glabrata mutant virulence in flies and mice.
- To develop a predictive model for mouse virulence based on fly survival data.
Main Methods:
- Infection of fruit flies and mice with a library of Candida glabrata mutants.
- Measurement of fly survival time as an index of virulence in invertebrates.
- Quantification of fungal burden in mouse organs to assess virulence in mammals.
- Comparison of data from both models to determine correlation and develop a predictive model.
Main Results:
- A good agreement was observed between fruit fly survival time and mouse fungal burden.
- A predictive model was developed to estimate mouse virulence from fly survival data.
- Cell wall integrity mutants showed attenuation in flies; MAP kinase pathway mutants exhibited defective virulence in both models.
- Mutants with reduced in vitro growth generally showed reduced virulence in flies.
Conclusions:
- Drosophila survival assays are a suitable model for predicting C. glabrata infection outcomes in mice.
- Pre-screening C. glabrata mutants in Drosophila can effectively estimate their virulence potential in mammalian hosts.
- The fruit fly model provides a valuable tool for prioritizing strains for further investigation in mammalian models.
