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Use of the genes in the Hog, Ras and cAMP pathway for treatment of fungal infection

机译:Hog,Ras和cAMP途径中的基因在真菌感染治疗中的应用

摘要

Provided herein are uses of genes for HOG, Ras and cAMP signal transduction pathways to treat fungal infection. To regulate the HOG pathway of Cryptococcus neoformans, roles of SSK1, TCO2, SSK2, PBS2, HOG1, ENA1 and NHA1 genes were investigated to find that a biosynthesis level of ergosterol is increased when these genes are inhibited. When the genes are inhibited, a large amount of ergosterol is distributed on a fungal cell membrane. Accordingly, since there are many working points of an ergosterol-binding antifungal agent, an efficiency of the ergosterol-binding antifungal agent can be considerably improved. To regulate the Ras and cAMP pathways of Cryptococcus neoformans, roles of RAS1, RAS2, CDC24, GPA1, CAC1, ACA1, PKA1, HSP12 and HSP122 genes were investigated to find that a sensitivity to a polyene- or azole-based drug is increased when these genes are inhibited. Therefore, an antifungal pharmaceutical composition including an inhibitor against the gene or protein encoded by the same can be used as an excellent combined antifungal agent which can reduce a conventional amount of an antifungal agent used and increase an efficiency.
机译:本文提供了HOG,Ras和cAMP信号转导途径的基因在治疗真菌感染中的用途。为了调节新型隐球菌的HOG途径,研究了SSK1,TCO2,SSK2,PBS2,HOG1,ENA1和NHA1基因的作用,发现当这些基因被抑制时,麦角固醇的生物合成水平会提高。当基因被抑制时,大量的麦角固醇会分布在真菌细胞膜上。因此,由于麦角固醇结合型抗真菌剂的工作点很多,因此可以显着提高麦角固醇结合型抗真菌剂的效率。为了调节新型隐球菌的Ras和cAMP途径,研究了RAS1,RAS2,CDC24,GPA1,CAC1,ACA1,PKA1,HSP12和HSP122基因的作用,发现其对多烯或当这些基因被抑制时,吡咯类药物就会增加。因此,可以将包含针对其编码的基因或蛋白质的抑制剂的抗真菌药物组合物用作优异的组合抗真菌剂,其可以减少常规的抗真菌剂的使用量并提高效率。

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