Voriconazole resistance mechanisms determination in Aspergillus section Nigri strains

Identifier:  TFG:1640

Handle: https://hdl.handle.net/20.500.11797/TFG1640

Authors:  Grau Prades, Núria

Abstract:
Invasive aspergillosis is an infectious disease caused by fungi of the Aspergillus genus that is lethal between 30 and 95% of the cases, according to the affected organs, and, in the last decades, its incidence has increased in parallel to the increase of immunosuppressed population. The treatment of choice against this disease includes the group of azole antifungals, but more and more Aspergillus isolates are able to withstand treatments with these compounds. While Aspergillus fumigatus is the main causative agent, other species of Aspergillus can also cause invasive aspergillosis, with Aspergillus fungi from the Nigri section being the second in incidence. Although the mechanisms of antifungal resistance are extensively studied in A. fumigatus, these are unknown in non-fumigatus species. In this work, strains of Aspergillus of the Nigri section with different degrees of sensitivity to voriconazole have been included and possible mechanisms of resistance have been studied such as the presence of mutations in the target protein of azoles, Cyp51A, the degradation of the antifungal by laccases and the increase in the amount of ergosterol in the membrane. It was not possible to establish a relationship between the mutations found and the resistance of the strains, but that was possible between the latter and the laccase activity. It was observed that the strains with greater resistance to voriconazole contained a higher concentration of ergosterol; with which it seems that the mechanisms of resistance to voriconazole of the Nigri section differ from those described in A. fumigatus.