Update and recent advances on azole resistance mechanisms in Aspergillus

Abstract Aspergillus fumigatus is the main causal agent of invasive aspergillosis (IA) although other species of the genus can also be the cause of IA, such as A. flavus, A. terreus, A. niger and related cryptic species. This infectious disease mainly affects immunosuppressed patients and it is linked to elevated mortality rates. Being voriconazole (VRC) 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 translates into a clinical failure increment as well. In this review, we summarize and discuss the azole resistance molecular data described to date in the most clinically prevalent sections of Aspergillus, comprising mechanisms that involve target proteins Cyp51 and ATP Binding Cassette (ABC) or Major Facilitator Superfamily (MFS) efflux pumps. Other resistance mechanisms proposed but not fully-characterized yet are also discussed.