Galleria mellonella as a model host to study virulence of Candida

Abstract

Candida spp. are among the most important human fungal pathogens, with infections ranging from relatively benign, superficial manifestation to life-threatening deep-seated candidiasis and disseminated disease. Different mouse models have been developed to recapitulate the different forms of candidiasis and murine models are considered to be the gold standard to study pathogenesis and analyze efficacy of antifungal treatment. However, economical, logistical, and ethical considerations limit the use of mammals in infection experiments, especially when the question at hand requires analysis of a large number of fungal strains. As an alternative approach, different invertebrate infection models have been developed, including Caenorhabditis elegans, Drosophila melanogaster, and larvae of the wax moth Galleria mellonella as hosts. G. mellonella are inexpensive to purchase and do not require specialized facilities for maintenance. The relatively large size of the larvae facilitates easy handling, injection of a defined inoculum, and sampling for downstream analyses. Furthermore, in contrast to other invertebrate hosts, G. mellonella larvae can be maintained at temperatures up to 37 °C, equivalent to the temperature in mammalian hosts.1 As temperature has been shown to affect expression of Candida virulence traits, this feature is important when assessing virulence of Candida strains.2 In addition, the larval immune system shows functional and structural similarity to the mammalian innate immune system: Pathogens are recognized by pathogen recognition receptors and can be phagocytosed by the insects’ hemocytes, the functional equivalent to mammalian neutrophils. Similar to neutrophils, hemocytes use reactive oxygen species and lytic enzymes to eliminate microorganisms.3 Antimicrobial peptides are produced by G. mellonella in response to infection and likely contribute to the host defense, as it has been shown for Candida epithelial infections using mammalian cells.4,5 Thus, it is not surprising that G. mellonella larvae are used increasingly as a model for Candida infections, for example to determine the virulence of genetically modified C. albicans strains6-11 and to determine the efficacy of antifungal treatment against both C. albicans and non-albicansCandida species.12-16