Mechanism of azole resistance in the Candida albicans strains isolated from vulvovaginal candidiasis / 中国感染与化疗杂志

ABSTRACT

Objective To investigate the resistance rates of the Candida albicans strains isolated from patients with vulvovaginal candidiasis to 5 antifungal agents and examine the mechanism of azole resistance in these strains.Methods A total of 1 646 C.albicans strains were collected in Obstetrics and Gynecology Hospital of Fudan University from January to December 2015.The resistance rates of these isolates to five antifungal agents were analyzed.Azole-resistant (n=30),dose dependent sensitive (S-DD) (n=13),and susceptible isolates (n=10) were randomly selected from the microbiology laboratories of three obstetrics and gynecology hospitals in Shanghai.The expression levels of drug efflux pump related gene CDR1,CDR2,MDR1 and drug target enzyme gene ERG11 were analyzed by real-time fluorescence quantitative polymerase chain reaction (PCR).At the same time,the ERG11 and ERG3 genes were amplified by PCR and sequenced,and analyzed for resistance-related mutations.Results Of the 1 646 C.albicans strains,5.2％,3.2％,2.5％ and 2.1％ were resistant to itraconazole,voriconazole,fluconazole and 5-fluorocytosine,respectively.All isolates were sensitive to amphotericin B.The expression of ERG11 gene was significantly higher in S-DD group and azole-resistant group than in azole-sensitive group (P＜0.05).The expression of CDR1,CDR2 and MDR1 did not show significant difference among the three groups.There were 13 missense mutations in the ERG11 gene,of which T123I,P98S and Y286D amino acid substitutions were newly discovered.Both T123I and Y132H were identified in 26 resistant isolates,of which 16 gene mutation was detected in two pan-azole-resistant isolates.Conclusions The C.albicans strains isolated from vulvovaginal candidiasis showed higher resistance rates to azole antifumgal agents than that to 5-fluorocytosine and amphotericin B.Mutation and over-expression ofERG11 gene may be one of the prevalent molecular mechanisms underlying azole resistance in C.albicans.were pan-azole-resistant.In addition,the ERG3 heterozygous