Contributions of spore secondary metabolites to UV-C protection and virulence varies in different Aspergillus fumigatus strains

Fungi are versatile organisms, which thrive in hostile environments, including the International Space Station (ISS), an environment with increased exposure to UV radiation. Several isolates of the human pathogen Aspergillus fumigatus have been found contaminating the ISS. In other fungi, secondary metabolites (SMs) called melanins have been shown to protect spores from UV radiation. To test the hypothesis that melanin and other known spore secondary metabolites (SMs) provide UV-C protection to A. fumigatus, we subjected SM spore mutants to UV-C radiation. We found DHN melanin mutants of two clinical A. fumigatus strains (Af293 and Cea17) but not a ISS isolated strain (IF1SW-F4) were more sensitive to UV-C than their respective WTs. Three additional spore metabolites were examined in Af293 where fumiquinazoline also showed UV-C protective properties, but two other spore metabolites, monomethylsulochrin and fumigaclavine, provided no UV-C protective properties. UV-C survival was also compromised by loss of the DNA repair protein AkuA which masked protective effects of fumiquinazoline. Further, because DHN melanin has been shown to shield A. fumigatus from the host immune system, we examined all DHN mutants for virulence in the zebrafish model of invasive aspergillosis. Following recent studies highlighting pathogenic variability of different A. fumigatus isolates, we found DHN melanin to be a virulence factor in CEA17 and IF1SW-F4 but not Af293. Taken together, this work suggests differential roles of specific spore metabolites across Aspergillus isolates and type of environmental stress.Importance: Fungal spores contain secondary metabolites that can protect them from a multitude of abiotic and biotic stresses. Conidia (asexual spores) of the human pathogen Aspergillus fumigatus synthesize several metabolites including melanin which has been reported to be important for virulence in this species and protective against UV radiation in other fungi. Here we investigate the role of melanin in diverse isolates of A. fumigatus and find variability in its ability to protect spores from UV-C radiation or impact virulence in a zebrafish model of invasive aspergillosis in two clinical and one space station strain. Further, we assess the role of other spore metabolites in a clinical strain of A. fumigatus and identify fumiquinazoline as an additional UV-C protective molecule. The results show differential roles of secondary metabolites in spore protection dependent on environment and strain of A. fumigatus. As protection from elevated levels of radiation is of paramount importance for future human outer space explorations, discovery of small molecules with radiation protective potential may result in developing novel safety measures for astronauts.