Aspergillus fumigatus is the most important pathogenic mold for humans. Invasive aspergillosis is a life-threatening infection affecting patients with depressed immune system (hematologic cancer patients, hematopoietic stem cell or solid-organ transplant recipients). Therapeutic options are limited and emergence of resistance associated with the widespread use of fungicides in agriculture and industry is a concern. Our research group investigates the mechanisms of resistance and stress response to antifungal drugs in Aspergillus fumigatus.
Aspergillus fumigatus exhibits some level of natural resistance to echinocandin drugs (e.g. caspofungin) with loss of efficacy at high drug concentrations (paradoxical effect). We investigate the network and intracellular pathways mediated by the heat shock proteins (Hsp90 and Hsp70) in this response.
Triazoles (e.g. voriconazole) represent the first-line treatment of invasive aspergillosis. Emergence of resistance due to well-defined mutations of the target gene (cyp51a) has been described. However, there are other mechanisms of stress adaptation which may be involved in the resistance to triazoles. We analyze the impact of prolonged triazole exposure of A. fumigatus strains on the development of resistance mediated by activation of efflux transporters.