Correlation between azole susceptibilities, genotypes, and ERG11 mutations in Candida albicans isolates associated with vulvovaginal candidiasis in China.
The relationship between susceptibilities to fluconazole and itraconazole and microsatellite CAI genotypes were examined from a total of 154 Candida albicans isolates (97 isolates causing vulvovaginitis in Chinese women and 6 vaginal isolates and 51 oral cavity isolates from asymptomatic carriers). The two dominant genotypes, CAI 30-45 (45 isolates) and CAI 32-46 (33 isolates), associated with vulvovaginitis showed significantly different azole susceptibility patterns with strong statistical support. CAI 32-46 isolates were usually less susceptible to both fluconazole and itraconazole than CAI 30-45 isolates and than the oral isolates with other diversified CAI genotypes. Remarkably different mutation patterns in the azole target gene ERG11 were correspondingly observed among C. albicans isolates representing different genotypes and sources. Isolates with the same or similar CAI genotypes usually possessed identical or phylogenetically closely related ERG11 sequences. Loss of heterozygosity in ERG11 was observed in all the CAI 32-46 isolates but not in the CAI 30-45 isolates and most of the oral isolates sequenced. Compared with the ERG11 sequence of strain SC5314 (X13296), two homozygous missense mutations (G487T and T916C) leading to two amino acid changes (A114S and Y257H) in Erg11p were found in CAI 32-46 isolates. The correlation between azole susceptibility and C. albicans genotype may be of potential therapeutic significance.
Ge
Shu-Hua
SH
Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Chaoyang District, Beijing 100101, China.
Wan
Zhe
Z
Li
Juan
J
Xu
Jianping
J
Li
Ruo-Yu
RY
Bai
Feng-Yan
FY
D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy / Q000382:microbiology*; D002681:China; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics*; D025141:Drug Resistance, Fungal / Q000235:genetics; D005260:Female; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D005838:Genotype; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA
D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D017964:Itraconazole; D015725:Fluconazole; D003577:Cytochrome P-450 Enzyme System