Linking calcium signaling and mitochondrial function in fungal drug resistance

The host range for Aspergillus fumigatus is wide, including mammals, aves, and insecta (stonebrood). This is linked to the significant adaptability of this important fungal pathogen. It is thermotolerant, able to grow up to 70 °C, and astonishingly also remains viable down to −20 °C (1). It is microaerophilic and a halophile; forms extensive biofilms, a problem for antifungal eradication in patients; and has >20 secondary metabolite biosynthetic clusters, some of the products of which have immunosuppressive and cytotoxic properties, such as gilotoxin. A. fumigatus also produces a large number of extracellular enzymes, many of which are allergenic, making this organism the only common human pathogen to also cause allergic disease. Further, its pathogenic capacity includes human lungs, airways, paranasal sinuses, and keratin-rich toenails, all in those without overt immune deficits. In immunocompromised people, invasion of lungs, skin, or paranasal sinuses is progressive and fatal, unless detected rapidly and optimally treated. A. fumigatus produces more allergenic proteins (n = ∼60) than any other living organism yet found. These allergens are produced in situ (usually in the airways) in those with asthma or cystic fibrosis, greatly worsening the patient’s condition, i.e., … [↵][1]1To whom correspondence may be addressed. Email: ddenning{at}manchester.ac.uk. [1]: #xref-corresp-1-1