Shaping the fungal adaptome--stress responses of Aspergillus fumigatus

Abstract

Aspergillus fumigatus as prime pathogen to cause aspergillosis has evolved as a saprophyte, but is also able to infect and colonise immunocompromised hosts. Based on the 'dual use' hypothesis of fungal pathogenicity, general characteristics have to be considered as unspecific virulence determinants, among them stress adaptation capacities. The susceptible, warm-blooded mammalian host represents a specific ecological niche that poses several kinds of stress conditions to the fungus during the course of infection. Detailed knowledge about the cellular pathways and adaptive traits that have evolved in A. fumigatus to counteract situations of stress and varying environmental conditions is crucial for the identification of novel and specific antifungal targets. Comprehensive profiling data accompanied by mutant analyses have shed light on such stressors, and nutritional deprivation, oxidative stress, hypoxia, elevated temperature, alkaline pH, extensive secretion, and, in particular during treatment with antifungals, cell membrane perturbations appear to represent the major hazards A. fumigatus has to cope with during infection. Further efforts employing innovative approaches and advanced technologies will have to be made to expand our knowledge about the scope of the A. fumigatus adaptome that is relevant for disease.