Invertebrates have been increasingly viewed as a valid model for virulence studies of human fungal pathogens as their virulence traits are likely conserved among different hosts. The caterpillar Galleria mellonella has been used as a heterologous host for a number of yeast pathogens. Here we have evaluated the possibility of applying this heterologous insect model to investigate the virulence trait of the filamentous fungal pathogen Aspergillus fumigatus: melanization. Melanization in A. fumigatus confers bluish-grey color to conidia and is a known virulence factor in mammal models. Surprisingly, conidial color mutants with deletions in the defined melanin biosynthesis gene cluster in B5233 background caused enhanced insect mortality. Insertional mutants in Af293 background producing conidia of previously identified colors and of novel colors were isolated and they also displayed a higher level of pathogenicity in the insect model, confirming the relationship between fungal melanization defects and enhanced virulence to the caterpillar. Exacerbated insect immune response induced by increased exposure of PAMPs and elevated levels of fungal secreted metalloproteinases may cause the increased mortality of the larvae infected with the color mutants. Our study underscores the importance of the knowledge about the insect innate immunity status in understanding fungal pathogenicity in insect models. This study also shows that the G. mellonella is a reproducible model for A. fumigatus that could become a valuable tool for studying fungal traits that are required for infections in both mammals and the insect. Additionally, our observations indicate the potential of using melanization defective mutants of natural insect fungal pathogens in the biological control of insect populations.
Full conference title:
6th International Aspergillus Meeting
- Asperfest 6 (2009)