Advances in Aspergillus fumigatus Pathobiology

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Background

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. However, compensatory mechanisms of cell wall remodeling are present and still poorly understood. Recent work has highlighted the key roles of intracellular signaling proteins or molecular chaperones, such as calcineurin or the heat shock protein 90 (Hsp90), in morphogenesis, stress responses, virulence and antifungal resistance. 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. The topic will focus on mechanisms of antifungal resistance, stress adaptation and virulence and the discovery of potential novel antifungal targets via a genetic and molecular approach. Articles related to the interactions of A. fumigatus with the host immune system in the development of IA are also welcomed. We intend to collect a large variety of article types, including complete and comprehensive reviews, expert opinions, hypotheses, and also original research articles illustrating new aspects and approaches on this topic. Through this project, we expect to open an opportunity for all scientists in the world dedicated to the pathobiology of this major human fungal pathogen to share their knowledge, experience and opinions and assemble their efforts in defining main research axes to progress in our quest of improved antifungal strategies against IA.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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