The problem of azole resistance
Azole resistance is an emerging problem in Aspergillus fumigatus, a saprophytic mold that causes a spectrum of diseases in animals and humans. Azole resistance is driven by the use of azole compounds in the environment. Surveillance studies show that resistance traits have migrated globally and management of azole-resistant aspergillus diseases is complex, with mortality rates of 90% to 100%. The key issue is understanding how A. fumigatus adapts to stress factors, such as azole exposure, both in its natural habitat and in the human host.
The integrated approach
To understand resistance selection, the life cycle of A. fumigatus needs to be investigated from its natural habitat to the disease it causes in patients: from molecule to man to population. This can be best investigated through an integrated approach combining expertise from mycologists, epidemiologists, evolutionary biologists and medical professionals. The Radboudumc and Wageningen University have an intensive collaboration aimed at understanding A. fumigates adaptation in different environments.
The course content
In this one-week course, we will address all aspects of azole resistance selection in A. fumigatus. We will address this problem from the point of view of the fungal cell in relation to possible adaptation strategies to (azole) stress, the role its reproduction mode, compensatory mutations and fitness. The epidemiology and dynamics related to spread of resistance traits in fungal populations will be discussed as well as the tools that are available to investigate these dynamics. Furthermore, the clinical implications of azole resistance and (individualised) management strategies will be discussed.
All abovementioned aspects will be explored from the perspective of the natural habitat of A. fumigatus as well as during human disease. Participants will also be encouraged to present and discuss own research data. Finally, we will formulate the main research questions that need to be addressed and the possible scientific approaches that can be followed.
Although the problem of resistance selection in a microorganism is not unique, resistance selection in moulds has unique characteristics that surpasses the medical research field. The course brings together experts in environmental mycology and human fungal disease, which is unique and will prove very stimulating and refreshing.