一种类似于核受体的途径,调节真菌中的多药性耐药性
Jitendra K Thakur1, Haribabu Arthanari, Fajun Yang
1Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA.
Nature
|April 4, 2008
概括
研究人员发现了真菌转录因子如何调节多药性耐药性 (MDR). 这项研究揭示了真菌和脊椎动物耐药性的保存机制,为难以治疗的真菌感染提供了新的治疗点.
科学领域:
- 医学真菌学 医学真菌学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 多种药物耐药性 (MDR) 复杂的机会性真菌感染在免疫受损患者的治疗.
- 通过真菌-转录因子对药物流量的升级是MDR的一个关键机制,但人们对其了解甚少.
研究的目的:
- 阐明病原性真菌中MDR背后的分子机制.
- 确定用于对抗耐药真菌感染的新型治疗点.
主要方法:
- 在Saccharomyces cerevisiae和Candida glabrata中研究了Pdr1p家族成员.
- 分析了调解器联合激活剂的Gal11p/MED15亚单元及其KIX域的作用.
主要成果:
- Pdr1p家族成员直接结合药物,诱导排泄表达和MDR.
- 在真菌调节器和脊椎动物PXR核受体之间发现了功能类比.
- 11p/MED15子单元及其KIX域在调节MDR方面发挥着至关重要的作用.
结论:
- 对真菌核受体类基因调节通路的详细机制理解.
- 确定了治疗多抗药性真菌感染的新型治疗点.
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