Functional Divergence of Hsp90 Genetic Interactions in Biofilm and Planktonic Cellular States.
Functional Divergence of Hsp90 Genetic Interactions in Biofilm and Planktonic Cellular States.
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DOI：
10.1371/journal.pone.0137947
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Cowen LE
中科院分区：
文献类型：
--
作者：
Diezmann S;Leach MD;Cowen LE
白色念珠菌是最普遍的机会性真菌病原体之一。它引起危及生命的血液感染的能力与形成生物膜的能力有关，生物膜本质上是耐药的扩散库。分子伴侣蛋白Hsp90是生物膜耐药和扩散的关键调节因子，它稳定了许多信号转导器。我们之前在浮游条件下鉴定了226个白色念珠菌Hsp90基因相互作用因子，其中56个参与转录调控。这些转录调节因子中的6个先前与生物膜的形成有关，这表明在浮游条件下发现的Hsp90基因相互作用可能在生物膜中具有功能意义。在这里，我们探索了Hsp90与这些转录因子遗传相互作用因子中的五个之间的关系：BCR1， MIG1, TEC1， TUP1和UPC2。我们在一个Hsp90条件表达菌株中删除了每个转录因子基因，并评估了生物膜的形成和形态发生。引人注目的是，Hsp90的缺失没有给突变体带来额外的生物膜缺陷。观察到一种相互作用，其中BCR1的缺失在Hsp90水平降低的同时增强了丝化。此外，尽管Hsp90在浮游条件下调节TEC1、TUP1和UPC2的表达，但它对生物膜没有影响。最后，我们探索了Hsp90和Tup1之间的物理相互作用，其WD40结构域表明它可能直接与Hsp90相互作用。Hsp90与Tup1形成稳定的复合物，不受温度或发育状态的影响。我们的研究结果阐明了Hsp90与成丝和生物膜形成的关键转录调控因子之间的物理相互作用，并表明Hsp90在浮游和生物膜细胞状态下具有不同的遗传相互作用。
Candida albicans is among the most prevalent opportunistic fungal pathogens. Its capacity to cause life-threatening bloodstream infections is associated with the ability to form biofilms, which are intrinsically drug resistant reservoirs for dispersal. A key regulator of biofilm drug resistance and dispersal is the molecular chaperone Hsp90, which stabilizes many signal transducers. We previously identified 226 C. albicans Hsp90 genetic interactors under planktonic conditions, of which 56 are involved in transcriptional regulation. Six of these transcriptional regulators have previously been implicated in biofilm formation, suggesting that Hsp90 genetic interactions identified in planktonic conditions may have functional significance in biofilms. Here, we explored the relationship between Hsp90 and five of these transcription factor genetic interactors: BCR1, MIG1, TEC1, TUP1, and UPC2. We deleted each transcription factor gene in an Hsp90 conditional expression strain, and assessed biofilm formation and morphogenesis. Strikingly, depletion of Hsp90 conferred no additional biofilm defect in the mutants. An interaction was observed in which deletion of BCR1 enhanced filamentation upon reduction of Hsp90 levels. Further, although Hsp90 modulates expression of TEC1, TUP1, and UPC2 in planktonic conditions, it has no impact in biofilms. Lastly, we probed for physical interactions between Hsp90 and Tup1, whose WD40 domain suggests that it might interact with Hsp90 directly. Hsp90 and Tup1 formed a stable complex, independent of temperature or developmental state. Our results illuminate a physical interaction between Hsp90 and a key transcriptional regulator of filamentation and biofilm formation, and suggest that Hsp90 has distinct genetic interactions in planktonic and biofilm cellular states.