Azole resistance mechanisms in Aspergillus: update and recent advances

Aspergillus fumigatus is the main causal agent of invasive aspergillosis (IA), however other species of the genus can also cause IA, such as Aspergillus flavus, Aspergillus terreus, Aspergillus niger and related cryptic species. This infectious disease mainly affects immunosuppressed patients and is linked to elevated mortality rates. As voriconazole is the treatment of choice for this condition, the relevant increase in the number of azole-resistant isolates in recent years has gathered alarming attention, as it also translates into an increase in clinical failures. In this review, we summarise and discuss the azole resistance molecular data described to date in the most clinically prevalent sections of Aspergillus, including mechanisms involving the target proteins Cyp51 and ATP-binding cassette (ABC) or major facilitator superfamily (MFS) efflux pumps. Other resistance mechanisms proposed but not yet fully characterised are also discussed.