Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering.
Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering.
复制标题
DOI：
10.1186/gb-2010-11-7-r77
复制
发表时间：
2010
期刊：
影响因子：
12.3
通讯作者：
Ideker T
中科院分区：
文献类型：
--
作者：
Kuo D;Tan K;Zinman G;Ravasi T;Bar-Joseph Z;Ideker T
真菌感染是一种新出现的健康风险，特别是那些涉及对抗真菌剂有耐药性的酵母菌的感染。为了了解酵母菌对抗真菌药物反应的机制范围，我们比较了三种进化上遥远的物种-酿酒酵母，光滑念珠菌和乳酸克鲁维酵母-在氟康唑暴露后随着时间的推移的基因表达模式。保守和分歧的表达模式进行了鉴定，使用一种新的软聚类算法，同时聚类数据从所有物种，同时纳入序列的直系。分析表明，互补的策略，以应付麦角固醇消耗唑类-酵母进口外源麦角固醇，念珠菌出口氟康唑，而克鲁维酵母没有，导致极端敏感性。在支持这一假设，我们发现，只有酵母菌在麦角固醇补充培养基中变得更加唑耐药，这取决于甾醇进口商Aus 1和Pdr 11，以及在克鲁维酵母中的甾醇进口商的转基因表达使其药物敏感性降低。我们比较了三种不同的酵母菌的氟康唑治疗使用一种新的聚类算法的动态转录反应。这种方法揭示了与氟康唑敏感性相关的监管程序之间的显着分歧。在未来，这种方法可能会被用来调查更广泛的物种，药物浓度和刺激，以揭示保守和不同的分子反应途径。
Fungal infections are an emerging health risk, especially those involving yeast that are resistant to antifungal agents. To understand the range of mechanisms by which yeasts can respond to anti-fungals, we compared gene expression patterns across three evolutionarily distant species - Saccharomyces cerevisiae, Candida glabrata and Kluyveromyces lactis - over time following fluconazole exposure. Conserved and diverged expression patterns were identified using a novel soft clustering algorithm that concurrently clusters data from all species while incorporating sequence orthology. The analysis suggests complementary strategies for coping with ergosterol depletion by azoles - Saccharomyces imports exogenous ergosterol, Candida exports fluconazole, while Kluyveromyces does neither, leading to extreme sensitivity. In support of this hypothesis we find that only Saccharomyces becomes more azole resistant in ergosterol-supplemented media; that this depends on sterol importers Aus1 and Pdr11; and that transgenic expression of sterol importers in Kluyveromyces alleviates its drug sensitivity. We have compared the dynamic transcriptional responses of three diverse yeast species to fluconazole treatment using a novel clustering algorithm. This approach revealed significant divergence among regulatory programs associated with fluconazole sensitivity. In future, such approaches might be used to survey a wider range of species, drug concentrations and stimuli to reveal conserved and divergent molecular response pathways.
登录
查看更多内容
影响因子：
4.3
作者：
Cai J;Xie D;Fan Z;Chipperfield H;Marden J;Wong WH;Zhong S
通讯作者：
Zhong S
影响因子：
64.8
作者：
Dujon, B;Sherman, D;Souciet, JL
通讯作者：
Souciet, JL
DOI：
10.1142/s0219720005001375
发表时间：
2005-08-01
影响因子：
1
作者：
Futschik, Matthias E.;Carlisle, Bronwyn
通讯作者：
Carlisle, Bronwyn
影响因子：
5.2
作者：
Barker, KS;Pearson, MM;Rogers, PD
通讯作者：
Rogers, PD
影响因子：
4.9
作者：
Ha, KC;White, TC
通讯作者：
White, TC