Cellular and molecular biology of Candida albicans estrogen response

Cellular and molecular biology of Candida albicans estrogen response
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DOI:
10.1128/ec.5.1.180-191.2006
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发表时间:
2006-01-01
期刊:
影响因子:
--
通讯作者:
Hoyer, LL
Hoyer, LL
中科院分区:
其他
文献类型:
--
作者:
Cheng, G;Yeater, KM;Hoyer, LL

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白色念珠菌是阴道念珠菌病最常见的病原体。宿主雌激素水平升高与阴道念珠菌病的发病率呈正相关。雌激素水平升高可能会影响宿主和/或真菌细胞。本研究探讨了17-β-雌二醇、17-α-雌二醇、乙炔基雌二醇和雌三醇在10(-5)至10(-10)M浓度范围内对几种白色念珠菌菌株的作用。将17-β-雌二醇或乙炔基雌二醇添加到C.白色念珠菌细胞引起形成芽管的细胞数量增加,芽管长度增加,呈剂量和菌株依赖性。添加17-α-雌二醇或雌三醇对培养细胞的芽管形成没有显著影响。暴露于外源性雌激素没有显着改变任何白色念珠菌培养物的生物量测试。雌激素处理的白色念珠菌细胞的转录谱显示在几种菌株-雌激素浓度-时间点组合中CDR 1和CDR 2的表达增加,表明这些基因对雌激素暴露最敏感。对缺乏CDR 1和CDR 2编码序列的菌株DSY 654的分析显示,在17-β-雌二醇存在下,芽管形成细胞的数量显著减少。在这些生长条件下,PDR 16是菌株DSY 654中上调最高的基因。这项研究的细胞生物学和基因表达数据导致了一个模型,该模型提出了磷脂和固醇代谢途径的组分如何相互作用以影响白色念珠菌芽管的形成和长度。
Candida albicans is the most common etiological agent of vaginal candidiasis. Elevated host estrogen levels and the incidence of vaginal candidiasis are positively associated. Elevated estrogen levels may affect host and/or fungal cells. This study investigates the effect of 17-beta-estradiol, 17-alpha-estradiol, ethynyl estradiol, and estriol on several C albicans strains at concentrations ranging from 10(-5) to 10(-10) M. The addition of 17-beta-estradiol or ethynyl estradiol to C. albicans cells caused an increase in the number of cells forming germ tubes and an increase in germ tube length in a dose- and strain-dependent manner. The addition of 17-alpha-estradiol or estriol did not have a significant effect on germ tube formation by the cultured cells. Exposure to exogenous estrogens did not significantly change the biomass of any C albicans culture tested. The transcriptional profile of estrogen-treated C albicans cells showed increased expression of CDRI and CDR2 across several strain-estrogen concentration-time point combinations, suggesting that these genes are the most responsive to estrogen exposure. Analysis of strain DSY654, which lacks the CDR1 and CDR2 coding sequences, showed a significantly decreased number of germ tube-forming cells in the presence of 17-beta-estradiol. PDR16 was the most highly up-regulated gene in strain DSY654 under these growth conditions. The cell biology and gene expression data from this study led to a model that proposes how components of the phospholipid and sterol metabolic pathways may interact to affect C albicans germ tube formation and length.