Advancements in animal models for preclinical testing of antifungal compounds: a focus on systemic candidiasis

Abstract

Systemic candidiasis, caused by Candida species such as Candida albicans and the super-bug Candida auris, poses a significant challenge in clinical treatment. The preclinical drug development process begins with in vitro testing to evaluate the fungistatic or fungicidal activity of potential compounds, followed by ex vivo studies to assess toxicity and immune modulation effects. The final step involves in vivo studies using animal models, particularly mice, to evaluate therapeutic efficacy, pharmacodynamics, and tolerability. Murine models, including gastrointestinal colonization and intravenous infection models, are crucial for studying C. albicans and Candida non-albicans infections. These models enable researchers to control variables such as fungal strain, inoculum dose, immunosuppression regimen, and the route of administration, facilitating the assessment of treatment outcomes. The intravenous infection model, in particular, is widely employed to evaluate the efficacy of antifungal agents. For C. auris, a highly resistant pathogen, immunosuppressed murine models are essential for inducing robust infections. While in vitro studies offer initial insights, in vivo models are indispensable for accurately replicating the complexity of human infections. Ultimately, these animal models bridge the gap between laboratory research and clinical applications, supporting the development of novel and effective antifungal treatments.