A Xenopus laevis Model for Systemic Fungal Infections

Xenopus laevis possesses both innate and adaptive immune systems, and we previously demonstrated its utility as an infection model for human bacterial pathogens. In this study, we investigated the utility of X. laevis as a model for fungal infections. The human-pathogenic fungi Candida albicans and Aspergillus fumigatus exhibited greater lethality in X. laevis than the nonpathogenic fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe. In frogs infected with C. albicans, viable fungal cells were detected in the blood and multiple organs early after infection, and gross white lesions and fungal hyphae were observed in the kidneys. C. albicans infection also increased renal expression of the proinflammatory cytokine gene s tnf and il1b, as well as the tissue injury-associated gene clu. Treatment with the antifungal agents amphotericin B and micafungin significantly improved the survival of C. albicans-infected frogs. Furthermore, a homozygous deletion mutant of UME6, a gene associated with C. albicans virulence, exhibited reduced lethality compared with the wild-type strain. These findings establish X. laevis as a vertebrate model of systemic fungal infection that enables the evaluation of fungal virulence, host responses, and the therapeutic efficacy of antifungal agents.