Our ambitions

Invasive fungal infections caused by the ubiquitous mold Aspergillus fumigatus are responsible for high morbidity and mortality in transplant patients. However, knowledge concerning the behavior of this filamentous fungus and the pathophysiology of A. fumigatus infections in this specific clinical setting remain elusive. Although there is increasing evidence that antimicrobial regimens recommended for preventing infectious diseases in these patients has the potential to promote the selection of less susceptible fungal isolates, how the immunosuppressive regimen may influence the biology of major fungal pathogens remains to be explored. On this basis, our research proposal will investigate on a broad scale the impact of the main immunosuppressive therapies used in transplant patients to prevent organ/cell rejection on A. fumigatus biology and genetic evolution. More specifically, this 36 months scientific program aims at (i) determining the ability of immunosuppressants to influence the physiology of A. fumigatus; (ii) characterizing phenotypic changes in A. fumigatus selected by  long term in vitro exposure to immunosuppressants and to decipher the underlying genetic determinants; and (iii) testing the clinical relevance of in vitro observations by conducting phenotype and genotype characterizations on A. fumigatus clinical isolates recovered from transplant patients. This 5 workpackage-project will be based on a multidisciplinary approach including complementary strategies such as adaptive laboratory evolution, phenotype analysis, whole-genome sequencing and cutting-edge genome editing techniques to decipher the incidence of long term exposure of currently used immunosuppressants on stress adaptation, drug resistance, host-pathogen interactions, and genomic variations in A. fumigatus. Providing answers to these questions is of overall importance as it can impact the incidence, progression of the disease, and overall the risk of therapeutic failure.