Examining the virulence of Candida albicans transcription factor mutants using Galleria mellonella and mouse infection models
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Published on: November 17, 2018
Sara Amorim-Vaz1, Eric Delarze1, Françoise Ischer1
1Institute of Microbiology, University of Lausanne and University Hospital of Lausanne Lausanne, Switzerland.
Abstract:
The aim of the present study was to identify Candida albicans transcription factors (TFs) involved in virulence. Although mice are considered the gold-standard model to study fungal virulence, mini-host infection models have been increasingly used. Here, barcoded TF mutants were first screened in mice by pools of strains and fungal burdens (FBs) quantified in kidneys. Mutants of unannotated genes which generated a kidney FB significantly different from that of wild-type were selected and individually examined in Galleria mellonella. In addition, mutants that could not be detected in mice were also tested in G. mellonella. Only 25% of these mutants displayed matching phenotypes in both hosts, highlighting a significant discrepancy between the two models. To address the basis of this difference (pool or host effects), a set of 19 mutants tested in G. mellonella were also injected individually into mice. Matching FB phenotypes were observed in 50% of the cases, highlighting the bias due to host effects. In contrast, 33.4% concordance was observed between pool and single strain infections in mice, thereby highlighting the bias introduced by the "pool effect." After filtering the results obtained from the two infection models, mutants for MBF1 and ZCF6 were selected. Independent marker-free mutants were subsequently tested in both hosts to validate previous results. The MBF1 mutant showed impaired infection in both models, while the ZCF6 mutant was only significant in mice infections. The two mutants showed no obvious in vitro phenotypes compared with the wild-type, indicating that these genes might be specifically involved in in vivo adapt.
Insights
This study identified Candida albicans transcription factors (TFs) involved in virulence. Discrepancies between mouse and Galleria mellonella models highlight host and pool effects, with MBF1 and ZCF6 showing potential in vivo roles.
Area of Science:
- Mycology
- Molecular Biology
- Infectious Diseases
Background:
- Candida albicans virulence relies on transcription factors (TFs).
- Mouse models are standard for fungal virulence, but mini-host models like Galleria mellonella are increasingly used.
- Understanding TF roles in virulence requires robust infection models.
Purpose of the Study:
- To identify Candida albicans transcription factors (TFs) critical for virulence.
- To compare the effectiveness of mouse and Galleria mellonella infection models for studying fungal virulence.
- To investigate host and pool effects on TF mutant phenotypes.
Main Methods:
- Screening barcoded TF mutants in mice and quantifying fungal burdens.
- Testing selected mutants individually in Galleria mellonella.
- Comparing mutant phenotypes across different experimental conditions (pool vs. single, mouse vs. G. mellonella).
Main Results:
- Significant discrepancies (only 25% matching phenotypes) were observed between mouse and G. mellonella models.
- Host effects explained 50% of phenotype discrepancies, while pool effects accounted for 33.4% in mouse models.
- MBF1 and ZCF6 mutants were identified; MBF1 showed impaired virulence in both models, while ZCF6 was significant only in mice.
Conclusions:
- Mouse and G. mellonella models yield different results for Candida albicans TF virulence studies.
- MBF1 and ZCF6 are potential virulence factors, with MBF1 being crucial in both models and ZCF6 specifically in mice.
- These TFs likely play roles in in vivo adaptation rather than in vitro growth.
