Establishment of a Mouse Intravenous Challenge Model for Predicting Virulence in Yarrowia lipolytica Disseminated Infection.

Abstract

Invasive fungal infections pose a significant health threat. Yarrowia lipolytica (formerly known as Candida lipolytica) is an opportunistic yeast with pathogenic potential, but its virulence and impact on the host remain poorly understood. This study aimed to investigate the infection characteristics associated with this relatively unknown pathogen by establishing reliable animal models. We developed intravenous challenge models in immunocompetent and immunosuppressed BALB/c mice by injecting fungal cells directly into the bloodstream. In immunocompetent mice, Y. lipolytica was effectively cleared even at the highest challenge dose of 1 × 10⁸ cells, resulting in minimal mortality. However, this clearance was accompanied by a significant elevation in peripheral blood cytokine levels. Three days post-infection, the fungal burden was highest in the lungs (P < 0.0001), followed by the spleen, kidneys, liver, and brain. In immunosuppressed mice, the mortality rate following Y. lipolytica infection significantly increased (P < 0.001), with the highest fungal burden consistently observed in the lungs. In the immunosuppressed model, clinical isolates exhibited a greater lung fungal burden compared to industrial isolate. In conclusion, Y. lipolytica is a low-virulence fungus that is challenging to establish as a fatal infection in immunocompetent hosts but exhibits a marked tropism for the lungs, where lung fungal burden serves as an effective indicator of virulence. This model may also provide critical insights for studying fungal pulmonary infection pathogenesis and the infection dynamics of Y. lipolytica, especially for immunocompromised patients.