HSP90 is a molecular chaperone that participates in folding, stabilization, activation, and assembly of several proteins, all of which are key regulators in cell signaling. In dimorphic pathogenic fungi such as Paracoccidioides brasiliensis, the adaptation to a higher temperature, acid pH and oxidative stress, is an essential event for fungal survival and also for the establishing of the infectious process. To further understand the role of this protein, we used antisense RNA technology to generate a P. brasiliensis isolate with reduced PbHSP90 gene expression (PbHSP90-aRNA). Reduced expression of HSP90 decreased yeast cell viability during batch culture growth and increased susceptibility to acid pH environments and imposed oxidative stress. Also, PbHSP90-aRNA yeast cells presented reduced viability upon interaction with macrophages. The findings presented here suggest a protective role for HSP90 during adaptation to hostile environments, one that promotes survival of the fungus during host-pathogen interactions.

译文

HSP90是一种分子伴侣,参与多种蛋白质的折叠,稳定,激活和组装,所有这些蛋白质都是细胞信号传导的关键调节剂。在双态致病性真菌 (例如巴西Paracoccidioides brasiliensis) 中,适应较高的温度,酸性pH和氧化应激是真菌存活以及建立感染过程的重要事件。为了进一步了解该蛋白的作用,我们使用反义RNA技术生成了具有降低PbHSP90基因表达 (PbHSP90-aRNA) 的巴西假单胞菌分离株。HSP90的表达降低了分批培养过程中酵母细胞的活力,并增加了对酸性pH环境的敏感性并施加了氧化应激。此外,PbHSP90-aRNA酵母细胞在与巨噬细胞相互作用时表现出降低的活力。此处提出的发现表明,HSP90在适应敌对环境期间具有保护作用,在宿主-病原体相互作用期间可促进真菌的存活。

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