Origins of Aspergillus fumigatus inoculum drives virulence in a murine model of invasive aspergillosis

Aspergillus fumigatus is the most prevalent filamentous fungal pathogen in humans, causing severe and often fatal invasive pulmonary aspergillosis (IPA) in immunocompromised patients. Disease is primarily initiated upon the inhalation of the ubiquitous airborne conidia – the initial inoculum – produced by A. fumigatus. These conidia are a complete developmental unit with an ability to exploit diverse environments, ranging from human lungs to agricultural composts. We utilized the common lab strain Af293 grown on the aromatic amino acid, L-tryptophan (Trp) to assess differences in toxin profile and virulence. Radial growth of wild type A. fumigatus on glucose minimal media (GMM) + L -Trp was significantly lower than radial growth on GMM alone at 3, 5, and 7 days post inoculation. The toxin profile of the conidia assessed by liquid chromatography–mass spectrometry (LCMS) and high performance liquid chromatography (HPLC) was altered when A. fumigatus conidia were grown on GMM + L -Trp, with significantly more amounts of gliotoxin and fumigaclavine when compared to GMM alone. Additionally, A. fumigatus conidia derived from growth on GMM + L -Trp were more virulent than when harvested from GMM alone in a triamcinolone murine model of IPA. Further deletions of enzymes involved in toxin production resulted in an altered virulence phenotype. These findings demonstrate that spore origins influence A. fumigatus toxin production and virulence. This research suggests the critical role environmental conditions may play in predisposing the conidia to thrive within the host and could allow for further risk assessments for immunocompromised individuals.