Aspergillus fumigatus CYP51 sequence: potential basis for fluconazole resistance

We have cloned and sequenced the Aspergillus fumigatus CYP51 gene which enc odes the target of azole antifungal agents, namely cytochrome P450 sterol 1 4 alpha -demethylase. Since A, fumigatus is intrinsically resistant to the widely used azole fluconazole, we compared its predicted CYP51 sequence to the CYP51 sequences from fluconazole-susceptible and resistant Candida albi cans, This analysis generated specific hypotheses regarding the basis for A . fumigatus fluconazole resistance: in particular, A. fumigatus residue Ile 301 corresponds to C, albicans residue Thr315 which is mutated to Ala in re sistant strains and is proposed to hydrogen bond with the sterol substrate.