| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
Candida albicans is the most important fungal pathogen of humans. Azoles are the most developed and widely used antifungal drugs in clinical treatments. The emergence of azole resistant strains in clinical isolates from individuals remains a serious problem in clinic. We investigated the cellular function of Sse1p, belonging to the heat shock protein 70 family, in Candida albicans. Drug susceptibility tests indicated that repression of SSE1 expression resulted in hypersensitivity to fluconazole and conferred fungicidal activity to fluconazole. We further found that Sse1p confered fluconazole tolerance by partially influencing the calcineurin signaling pathway. Involvement of Sse1p in fluconazole tolerance was also observed in an azole insensitive pathogenic fungus C. glabrata. Our results indicate that compromising Sse1p functions offers an alternative strategy for increasing the effectiveness of fluconazole in the treatment of C. albicans and C. glabrata infections.
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