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Aspergillus fumigatus is the leading invasive mold pathogens in humans. The first line of treatment for invasive A. fumigatus infections are the triazole antifungals that inhibit Erg11/Cyp51 lanosterol demethylase activity, blocking ergosterol biosynthesis.

In recent years, triazole resistance of A. fumigatus has been increasingly reported, both as a result of widespread agricultural use of fungicidal triazoles and long-term treatment in patients with chronic aspergillosis. To date, the most common triazole resistance mechanisms in A. fumigatus are alterations in the erg11A/cyp51A gene or promoter, followed by overexpression of efflux pumps and mutations in hmg1, encoding HMG-CoA reductase. To identify novel triazole resistance mechanisms, we passaged A …