This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mylonakis, E. Articles by Diener, A. Search for Related Content PubMed PubMed Citation Articles by Mylonakis, E. Articles by Diener, A.

Galleria mellonella as a Model System To Study Cryptococcus neoformans Pathogenesis

Division of Infectious Diseases,¹ Department of Molecular Biology,² Center for Immunology and Inflammatory Diseases,³ Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Massachusetts 02114,⁴ Department of Molecular Genetics and Microbiology,⁵ Division of Infectious Diseases,⁶ Department of Medicine,⁷ Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710,⁸ Department of Microbiology and Molecular Genetics,⁹ Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115,¹⁰

Received 27 November 2004/ Returned for modification 7 January 2005/ Accepted 26 January 2005

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.

Editor: T. R. Kozel

This article has been cited by other articles:

• Seed, K. D., Dennis, J. J. (2008). Development of Galleria mellonella as an Alternative Infection Model for the Burkholderia cepacia Complex. Infect. Immun. 76: 1267-1275 [Abstract] [Full Text]  
• Rutherford, J. C., Lin, X., Nielsen, K., Heitman, J. (2008). Amt2 Permease Is Required To Induce Ammonium-Responsive Invasive Growth and Mating in Cryptococcus neoformans. Eukaryot Cell 7: 237-246 [Abstract] [Full Text]  
• Fan, W., Idnurm, A., Breger, J., Mylonakis, E., Heitman, J. (2007). Eca1, a Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase, Is Involved in Stress Tolerance and Virulence in Cryptococcus neoformans. Infect. Immun. 75: 3394-3405 [Abstract] [Full Text]  
• Park, S. Y., Kim, K. M., Lee, J. H., Seo, S. J., Lee, I. H. (2007). Extracellular Gelatinase of Enterococcus faecalis Destroys a Defense System in Insect Hemolymph and Human Serum. Infect. Immun. 75: 1861-1869 [Abstract] [Full Text]  
• Altincicek, B., Linder, M., Linder, D., Preissner, K. T., Vilcinskas, A. (2007). Microbial Metalloproteinases Mediate Sensing of Invading Pathogens and Activate Innate Immune Responses in the Lepidopteran Model Host Galleria mellonella. Infect. Immun. 75: 175-183 [Abstract] [Full Text]  
• Idnurm, A., Giles, S. S., Perfect, J. R., Heitman, J. (2007). Peroxisome Function Regulates Growth on Glucose in the Basidiomycete Fungus Cryptococcus neoformans. Eukaryot Cell 6: 60-72 [Abstract] [Full Text]  
• Steinbach, W. J., Cramer, R. A. Jr., Perfect, B. Z., Asfaw, Y. G., Sauer, T. C., Najvar, L. K., Kirkpatrick, W. R., Patterson, T. F., Benjamin, D. K. Jr., Heitman, J., Perfect, J. R. (2006). Calcineurin Controls Growth, Morphology, and Pathogenicity in Aspergillus fumigatus.. Eukaryot Cell 5: 1091-1103 [Abstract] [Full Text]  
• Tang, R. J., Breger, J., Idnurm, A., Gerik, K. J., Lodge, J. K., Heitman, J., Calderwood, S. B., Mylonakis, E. (2005). Cryptococcus neoformans Gene Involved in Mammalian Pathogenesis Identified by a Caenorhabditis elegans Progeny-Based Approach. Infect. Immun. 73: 8219-8225 [Abstract] [Full Text]