Relationship between antifungal resistance of fluconazole resistant Candida albicans and mutations in ERG11 gene.
BACKGROUND
The cytochrome P450 lanosterol 14alpha-demethylase (Erg11p) encoded by ERG11 gene is the primary target for azole antifungals. Changes in azole affinity of this enzyme caused by amino acid substitutions have been reported as a mechanism of azole antifungal resistance. This study aimed to investigate the relationship between amino acid substitutions in Erg11p from fluconazole resistant Candida albicans (C. albicans) isolates and their cross-resistance to azoles.


METHODS
Mutations in ERG11 gene were screened in 10 clinical isolates of fluconazole resistant C. albicans strains. DNA sequence of ERG11 was determined by PCR based DNA sequencing.


RESULTS
In the 10 isolates, 19 types of amino acid substitutions were found, of which 10 substitutions (F72S, F103L, F145I, F198L, G206D, G227D, N349S, F416S, F422L and T482A) have not been reported previously. Mutations in ERG11 gene were detected in 9 isolates of fluconazole resistant C. albicans, but were not detected in 1 isolate.


CONCLUSIONS
Although no definite correlation was found between the type of amino acid substitutions in Erg11p and the phenotype of cross-resistance to azoles, the substitutions F72S, F145I and G227D in our study may be highly associated with resistance to azoles because of their special location in Erg11p.
Feng
Li-juan
LJ
Department of Dermatology, Peking University First Hospital; Research Center for Medical Mycology, Peking University, Beijing 100034, China.
Wan
Zhe
Z
Wang
Xiao-hong
XH
Li
Ruo-yu
RY
Liu
Wei
W
D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D009154:Mutation
D000935:Antifungal Agents; D005656:Fungal Proteins; C465525:cytochrome P-450 CYP51, Candida albicans; D015725:Fluconazole; D003577:Cytochrome P-450 Enzyme System