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,所有这些都是细胞信号传导中的关键调控因子。在双态致病性真菌(如巴西副球菌)中,适应更高的温度,酸性pH和氧化应激,是真菌存活和建立感染过程的重要事件。为了进一步了解该蛋白的作用,我们使用了反义RNA技术来生成具有降低的PbHSP90基因表达的巴西假单胞菌分离物(PbHSP90-aRNA)。 HSP90的表达降低会降低分批培养物生长过程中酵母细胞的活力,并增加对酸性pH环境的敏感性和施加的氧化应激。同样,PbHSP90-aRNA酵母细胞与巨噬细胞相互作用后,活力降低。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,可在宿主与病原体相互作用期间促进真菌的存活。

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