Advances in Aspergillus fumigatus pathobiology

Overview & Synopsis

Aspergillus fumigatus is a human fungal pathogen that causes invasive aspergillosis (IA), a major infectious cause of death in the expanding population of immunocompromised individuals such as cancer patients and transplant recipients. The mortality of IA remains high (30-70%) and emerging resistance to triazoles, the first-line antifungal drug class, is of particular concern. Second-line therapies for IA are limited by their toxicity (polyenes) or their lack of fungicidal activity (echinocandins). Identification of novel antifungal targets is an urgent need for improving the outcome of IA. A. fumigatus is a filamentous fungus exhibiting a complex developmental cycle and elaborated mechanisms of adaptation to allow the initiation and progression of infection in the human host. The fungal cell wall, with its unique and dynamic structure, is crucial for protecting cell integrity and evading the host immune system, also contributing to biofilm formation and virulence, and thus representing an ideal antifungal target. The emergence of azole resistance implies various and complex mechanisms that need to be further elucidated. Other important processes, such as biosynthetic pathways and toxin/metabolite production are important for fungal survival and propagation in the host environment, ultimately leading to disease. Moreover, the host immune response is a determinant factor in influencing the course of infection. The objective of this topic issue is to provide an overview of the recent advances in our understanding of A. fumigatus pathobiology and of IA pathogenesis to outline future research.