Aspergillus fumigatus, a saprotroph widespread in nature, is typically found in soil and decaying organic matter, such as compost heaps, where it plays an essential role in carbon and nitrogen recycling.

In 2008, A. fumigatus was shown to possess a fully functional sexual reproductive cycle, 145 years after its original description by Fresenius.

In immunocompromised individuals, such as organ transplant recipients and people with AIDS or leukemia, the fungus is more likely to become pathogenic, over-running the host's weakened defenses and causing a range of diseases generally termed aspergillosis.

Due to the recent increase in the use of immunosuppressants to treat human illnesses, it is estimated that A. fumigatus may be responsible for over 600,000 deaths annually with a mortality rate between 25 and 90%.

[13] Neutrophils are essential for aspergillosis resistance, as demonstrated in neutropenic individuals, and are capable of sequestering both conidia and hyphae through distinct, non-phagocytic mechanisms.

[11][13] In addition to these cell-mediated mechanisms of elimination, antimicrobial peptides secreted by the airway epithelium contribute to host defense.

These conidia emerge from dormancy and make a morphological switch to hyphae by germinating in the warm, moist, nutrient-rich environment of the pulmonary alveoli.

[11][14] The process of angioinvasion causes endothelial damage and induces a proinflammatory response, tissue factor expression and activation of the coagulation cascade.

[14] As is common with tumor cells and other pathogens, the invasive hyphae of A. fumigatus encounters hypoxic (low oxygen levels, ≤ 1%) micro-environments at the site of infection in the host organism.

[17][18][19] Current research suggests that upon infection, necrosis and inflammation cause tissue damage which decreases available oxygen concentrations due to a local reduction in perfusion, the passaging of fluids to organs.

[18] The exact implications of hypoxia on fungal pathogenesis is currently unknown, however these low oxygen environments have long been associated with negative clinical outcomes.

Two highly characterized sterol-regulatory element binding proteins, SrbA and SrbB, along with their processing pathways, have been shown to impact the fitness of A. fumigatus in hypoxic conditions.

The transcription factor SrbA is the master regulator in the fungal response to hypoxia in vivo and is essential in many biological processes including iron homeostasis, antifungal azole drug resistance, and virulence.

In contrast, targeted mutation of sidA, the first gene in the siderophore biosynthesis pathway, proved siderophore-mediated iron uptake to be essential for virulence.

[28][29] Mutation of the downstream siderophore biosynthesis genes sidC, sidD, sidF and sidG resulted in strains of A. fumigatus with similar decreases in virulence.

[32] Aspergillus fumigatus produces and secretes elastases, proteases that cleave elastin in order to break down these macromolecular polymers for uptake.

[44] Genome sequencing has revealed 40 potential genes involved in secondary metabolite production including mycotoxins, which are produced at the time of sporulation.

[40] LaeA influences the expression of 9.5% of the A. fumigatus genome, including many secondary metabolite biosynthesis genes such as nonribosomal peptide synthetases.

[50] The ΔlaeA mutant showed increased susceptibility to macrophage phagocytosis and decreased ability to kill neutrophils ex vivo.

Azole drugs such as voriconazole, itraconazole, and imidazole kill fungi by inhibiting the production of ergosterol—a critical element of fungal cell membranes.