Directed evolution of the pathogenic mold Aspergillus fumigatus reveals novel triazole-resistance genes

Aspergillus fumigatus is the leading cause of invasive mold infections in immunocompromised patients. Current antifungal treatment primarily depends on the triazole antifungals, which act by noncompetitively inhibiting Erg11/Cyp51, a key enzyme in the ergosterol biosynthetic pathway. However, resistance is emerging at an increasing rate, reducing treatment efficacy and patient survival. To identify additional elements in triazole resistance, we evolved A. fumigatus wild-type and mutant delta-cyp51A strains under increasing voriconazole concentrations.