Galleria mellonella as a Model System To Study Cryptococcus neoformans Pathogenesis

Evaluation of Cryptococcus neoformans virulence in a number of nonmammalian hosts suggests that C. neoformans is a nonspecific pathogen. We used the killing of Galleria mellonella (the greater wax moth) caterpillar by C. neoformans to develop an invertebrate host model system that can be used to stu...

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Bibliographic Details
Published in:Infection and Immunity 2005-07, Vol.73 (7), p.3842-3850
Main Authors: Mylonakis, Eleftherios, Moreno, Roberto, El Khoury, Joseph B, Idnurm, Alexander, Heitman, Joseph, Calderwood, Stephen B, Ausubel, Frederick M, Diener, Andrew
Format: Article
Language:English
Subjects:
amphotericin B
animal disease models
Animals
Antifungal Agents - pharmacology
Biological and medical sciences
Cryptococcus neoformans
Cryptococcus neoformans - drug effects
Cryptococcus neoformans - genetics
Cryptococcus neoformans - pathogenicity
drug therapy
flucytosine
Fundamental and applied biological sciences. Psychology
Fungal and Parasitic Infections
Galleria mellonella
genes
hemocoel
hemocytes
Hemocytes - physiology
larvae
Microbiology
Miscellaneous
Moths - microbiology
Mycology
mycoses
pathogenesis
pathogenicity
phagocytosis
Virulence
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Summary:Evaluation of Cryptococcus neoformans virulence in a number of nonmammalian hosts suggests that C. neoformans is a nonspecific pathogen. We used the killing of Galleria mellonella (the greater wax moth) caterpillar by C. neoformans to develop an invertebrate host model system that can be used to study cryptococcal virulence, host immune responses to infection, and the effects of antifungal compounds. All varieties of C. neoformans killed G. mellonella. After injection into the insect hemocoel, C. neoformans proliferated and, despite successful phagocytosis by host hemocytes, killed caterpillars both at 37°C and 30°C. The rate and extent of killing depended on the cryptococcal strain and the number of fungal cells injected. The sequenced C. neoformans clinical strain H99 was the most virulent of the strains tested and killed caterpillars with inocula as low as 20 CFU/caterpillar. Several C. neoformans genes previously shown to be involved in mammalian virulence (CAP59, GPA1, RAS1, and PKA1) also played a role in G. mellonella killing. Combination antifungal therapy (amphotericin B plus flucytosine) administered before or after inoculation was more effective than monotherapy in prolonging survival and in decreasing the tissue burden of cryptococci in the hemocoel. The G. mellonella-C. neoformans pathogenicity model may be a substitute for mammalian models of infection with C. neoformans and may facilitate the in vivo study of fungal virulence and efficacy of antifungal therapies.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.73.7.3842-3850.2005