Correlation between Azole Susceptibilities, Genotypes, and ERG11 Mutations in Candida albicans Isolates Associated with Vulvovaginal Candidiasis in China

Correlation between Azole Susceptibilities, Genotypes, and ERG11 Mutations in Candida albicans Isolates Associated with Vulvovaginal Candidiasis in China
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DOI:
10.1128/aac.00118-10
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发表时间:
2010-08-01
影响因子:
4.9
通讯作者:
Bai, Feng-Yan
Bai, Feng-Yan
中科院分区:
医学2区
文献类型:
--
作者:
Ge, Shu-Hua;Wan, Zhe;Bai, Feng-Yan

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从154株白色念珠菌(97株引起中国女性外阴阴道炎,6株阴道分离株和51株无症状携带者的口腔分离株)中检测了对氟康唑和伊曲康唑的敏感性与微卫星CAI基因型之间的关系。与外阴阴道炎相关的两种优势基因型CAI 30-45(45株)和CAI 32-46(33株)显示出显著不同的唑类药物敏感性模式,具有强有力的统计学支持。CAI 32-46菌株对氟康唑和伊曲康唑的敏感性通常低于CAI 30-45菌株和其他不同CAI基因型的口腔分离株。相应地,在C.代表不同基因型和来源的白色念珠菌分离株。具有相同或相似CAI基因型的分离物通常具有相同或遗传学上密切相关的ERG 11序列。在所有CAI 32-46分离株中观察到ERG 11的杂合性缺失,但在CAI 30-45分离株中未观察到,并且大多数口腔分离株测序。与SC 5314株(X13296)的ERG 11基因序列比较,CAI 32-46株的ERG 11基因有两个错义突变(G487 T和T916 C),导致Erg 11 p的两个氨基酸改变(A114 S和Y257 H)。唑类药物敏感性与C.白念珠菌基因型可能具有潜在的治疗意义。
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.