Relationship Between Gene CYP51 and Clinical Azole-resistant Candida albicans Isolates / 中华医院感染学杂志

ABSTRACT

OBJECTIVE To explore the relationship between the point mutations of gene CYP51 and the azole-resistance mechanism in clinical Candida albicans isolates.METHODS The paper diffusion test and NCCLS M-27 protocols were used to screen the fluconazole-resistant and itraconazole-resistant C.albicans clinical isolates.Gene CYP51 of two azole-resistant C.albicans clinical strains(2007H and 2007T strains) was amplified by three pairs of primers,respectively.The PCR products purified were sequenced,and compared with the nucleotide sequences of C.albicans(accession No.X13296) to find out the mutation sites.RESULTS The nucleotide sequence analysis showed that there were both significant point mutations and silent mutations in gene CYP51 from two azole-resistant isolates of C.albicans.Seven mutations previously described,F105L,K128T,Y132H,T199I,R267H,G464S,and R467K,were identified in the two strains.The animo acid substitutions of Y132H and R467K,known to contribution to azole resistance,were detected in both 2007H strain and 2007T strain.Four novel mutations,including F71L,W244R,T311N and T352I,were simultanously identified.Nine silent mutations appeared in two isolates.CONCLUSIONS In this survey,the two azole-resistant C.albicans clinical isolates contained more than one mutation in gene CYP51 that is associated with azole resistance.Four novel mutations of CYP51 may be associated with the resistance of C.albicans to azoles.And the mechanisms need to be further studied in detail.