ABSTRACT
Objective: To investigate the azole susceptibility of Candida albicans ( C. albicans) from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance. Methods: Three hundred and two clinical isolates of Candida species were collected. Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 17 isolates of C. albicans (2 susceptibles, 5 dose-dependent resistants and 10 resistants) were amplified and sequenced. Results: Of the 302 isolates collected, 70.2% were C. albicans, of which 8.5%, 3.8% and 4.2% were resistant to fluconazole, itraconazole and voriconazole, respectively. In total, 27 missense mutations were detected in ERG11 genes from resistant/susceptible dose-dependent isolates. Among them, Y132H, A114S, and Y257H substitutions were most prevalent and were known to cause fluconazole resistance. G464S and F72S also have been proved to cause fluconazole resistance. Two novel substitutions (T285A, S457P) in hotspot regions were identified. Conclusions: Twenty seven mutations in the ERG11 gene were identified in azole-resistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of vulvovaginal candidosis. The relationship of two novel substitutions (T285A, S457P) with fluconazole resistance needs to be further verified by site-directed mutagenesis.
ABSTRACT
OBJECTIVE@#To analyse the var gene repertoire and characterise the chondroitin sulphate A (CSA)-binding activity of the Duffy-binding like (DBL) domains encoded by the var2csa gene of a Plasmodium falciparum (P. falciparum) isolate in Hainan Province, China.@*METHODS@#The sequences of var DBL1 regions were PCR-amplified, sequenced and the sequence characteristics was bioinformatically analysed. Recombinant proteins encoded by the var2csa genes were expressed and purified. The binding activities of the recombinant proteins to CSA receptor was detected by ELISA assays.@*RESULTS@#Fifty six unique DBL α sequences were obtained, and the sequences represented similar diversity to the var genes of the genome parasite 3D7. There are two var2csa genes in the P. falciparum isolated from Hainan Province. Unlike in other falciparum parasites such as HB3, the two var2csa genes are more diverged. The receptor-binding capacity of DBL-5ε and DBL-6ε domains of HN var2CSA was studied.@*CONCLUSIONS@#This work represented the diversity of var genes of a P. falciparum isolate in China.