Impact of the cystic fibrosis pulmonary microenvironment on the physiology of Aspergillus fumigatus and Scedosporium apiospermum and their interactions with bronchial epithelial cells – MuCEScAp

Aspergillus fumigatus and Scedosporium apiospermum are the main moulds found in the lungs of patients with cystic fibrosis. This fungal colonisation illustrates the ability of these fungi to adapt to an unfavourable environment, characterised by changes in the properties of pulmonary mucus. Given their ability to cause serious infections in the presence of an immune deficiency, it is crucial to gain a better understanding of how these fungi manage to survive under such conditions. This is all the more important given that lung transplantation, still regarded as the last resort for patients with cystic fibrosis, requires the use of immunosuppressants, which expose patients to a risk of invasive, and sometimes fatal, infection. It is therefore necessary to discover new, more effective treatments, which requires a better understanding of the mechanisms underlying the pathogenicity of these fungi. Our project aims to gain a better understanding of how the bronchial microenvironment of people with cystic fibrosis influences the behaviour of the fungi A. fumigatus and S. apiospermum. To this end, these two fungi will be cultured under three different conditions: a standard medium, a medium replicating a healthy lung, and another mimicking lungs affected by cystic fibrosis; we will then investigate how these conditions alter the fungi’s physiology and their susceptibility to antifungal agents. We will also analyse how these fungi interact with healthy human lung cells and with those carrying the mutation responsible for cystic fibrosis. Using an advanced technique, we will be able to examine in detail the responses of the fungi and the lung cells. This research will lead to a better understanding of fungal infections in the context of cystic fibrosis and, ultimately, pave the way for new treatments. This project is coordinated by Dr Dorra Elhaj Mahmoud (IRF) and supported by the organisations Vaincre la Mucoviscidose, the Association Grégory Lemarchal and the Académie Pulsar.