Aspergillus fumigatus establishes infection in zebrafish by germination of phagocytized conidia, while Aspergillus niger relies on extracellular germination.

Among opportunistically pathogenic filamentous fungi of the Aspergillus genus, Aspergillus fumigatus stands out as a drastically more prevalent cause of infection than others. Utilizing the zebrafish embryo model, we applied a combination of non-invasive real-time imaging and genetic approaches to compare the infectious development of A. fumigatus with that of the less pathogenic A. niger. We found that both species evoke similar immune cell migratory responses, but A. fumigatus is more efficiently phagocytized than A. niger. Though efficiently phagocytized, A. fumigatus conidia retains the ability to germinate and form hyphae from inside macrophages leading to serious infection even at relatively low infectious burdens. By contrast, A. niger appears to rely on extracellular germination, and rapid hyphal growth to establish infection. Despite these differences in the mechanism of infection between the species, galactofuranose mutant strains of both A. fumigatus and A. niger display attenuated pathogenesis. However, deficiency in this cell wall component has a stronger impact on A. niger, which is dependent on rapid extracellular hyphal growth. In conclusion, we uncover differences in the interaction of the two fungal species with innate immune cells, noticeable from very early stages of infection, which drive a divergence in their route to establishing infections.